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Gastric Cancer Cells (gastric + cancer_cell)

Distribution by Scientific Domains

Medical Sciences	89%
Chemistry	8%

Distribution within Medical Sciences

Oncology & Radiotherapy	48%
Gastroenterology & Hepatology	19%
6 Other Subdomains	33%

Kinds of Gastric Cancer Cells

human gastric cancer cell

Terms modified by Gastric Cancer Cells

gastric cancer cell line

Selected Abstracts

The Effects of Cyclooxygenase2,ProstaglandinE2 Pathway on Helicobacter pylori -Induced Urokinase-Type Plasminogen Activator System in the Gastric Cancer Cells

HELICOBACTER, Issue 3 2008
Junichi Iwamoto
Abstract Background:, Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) play an important role in the destruction of the extracellular matrix and basement membrane. The induction of uPA and uPAR in the gastric cancer cells with H. pylori has been demonstrated previously. The involvement of COX-2-PGE2 pathway in the uPA system (uPA and uPAR) expression is unclear. Methods:, Gastric cancer cells (MKN45) were co-cultured with H. pylori standard strain (NCTC11637). The specific inductions of uPA and uPAR mRNA were examined by reverse transcription-polymerase chain reaction amplification. The secreted uPA antigen was measured by ELISA. To evaluate the involvement of COX-2 and PGE2 pathway in H. pylori -induced uPA and uPAR expressions, we examined the effects of COX-2 inhibitor and PGE2 receptor antagonist on H. pylori -induced uPA and uPAR expression in the gastric cancer cells. Results:, The expressions of both uPA and uPAR mRNAs in the gastric cancer cells increased obviously (12-fold and 3-fold, respectively) with H. pylori stimulation. The amount of uPA antigen into the culture medium increased dramatically with H. pylori stimulation. The COX-2 expression level in the gastric cancer cells increased remarkably with H. pylori stimulation. H. pylori -induced uPA and uPAR expression levels were suppressed with COX2 inhibitor treatment. The amount of PGE2 antigen into the culture medium increased dramatically 24 hours after H. pylori stimulation. The gastric cancer cells expressed EP2 and EP4 subtypes. EP2 receptor antagonist suppressed the H. pylori -induced uPA and uPAR expressions in the gastric cancer cells. Conclusions:, Our results indicated that COX2-PGE2 pathway may be involved in H. pylori- associated uPA and uPAR induction, and that COX-2 inhibitor or EP2 receptor antagonist may inhibit angiogenesis and tumor invasion via suppression of the uPA system. [source]

ChemInform Abstract: Novel Anthraquinone Derivatives: Synthesis via Click Chemistry Approach and Their Induction of Apoptosis in BGC Gastric Cancer Cells via Reactive Oxygen Species(ROS)-Dependent Mitochondrial Pathway.

CHEMINFORM, Issue 17 2009
Shaoru Wang
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source]

The Effects of Cyclooxygenase2,ProstaglandinE2 Pathway on Helicobacter pylori -Induced Urokinase-Type Plasminogen Activator System in the Gastric Cancer Cells

Mechanism of Action of Low Recurrence of Gastritis Caused by Helicobacter pylori with the Type II Urease B Gene

HELICOBACTER, Issue 2 2004
Md. Badruzzaman
ABSTRACT Background., Low recurrence of gastritis is seen in patients infected with Helicobacter pylori carrying the type II urease B gene, compared with H. pylori carrying types I and III. The underlying mechanism has been studied in terms of the urease activity and interleukin (IL)-8 production capacity of different strains of H. pylori. Materials and Methods., Forty-five patients infected with different strains of H. pylori (type I; 15, type II; 15 and type III; 15) were enrolled in the study. H. pylori was isolated from gastric mucosa and cultured in the presence of urea at pH 5.5 to evaluate urease activity. The capacity of different strains of H. pylori to induce IL-8 mRNA and IL-8 from a human gastric cancer cell line and human peripheral blood mononuclear cells was evaluated. Results., The urease activity of type II H. pylori[523 ± 228 µg of ammonia/dl/108 colony-forming units (CFU)/ml] was significantly lower than that of type I (1355 ± 1369 µg of ammonia/dl/108 CFU/ml) and type III (1442 ± 2229 µg of ammonia/dl/108 CFU/ml) (p < .05). Gastric cancer cells cocultured with type II H. pylori produced lower levels of IL-8 mRNA compared with type I and type III H. pylori. The levels of IL-8 were also significantly lower in cultures induced by type II H. pylori compared with those induced by type I and type III H. pylori. Peripheral blood mononuclear cells also produced lower levels of IL-8 when cocultured with type II compared with type I H. pylori. Conclusions., These results indicate that both the lower level of urease activity and the low IL-8-inducing capacity of type II H. pylori might underlie the lower recurrence rate of gastritis caused by type II H. pylori. [source]

Retraction: Blockage of intracellular proton extrusion with proton pump inhibitor induces apoptosis in gastric cancer

CANCER SCIENCE, Issue 1 2008
Marie Yeo
The following article from Cancer Science, ,Blockage of intracellular proton extrusion with proton pump inhibitor induces apoptosis in gastric cancer' by Marie Yeo, Dong-Kyu Kim, Hee Jin Park, Sung Won Cho, Jae Youn Cheong and Kwang Jae Lee (doi: 10.1111/j.1349-7006.2007.00642.x), published online on 23 October 2007 on Blackwell Synergy (http://www.blackwell-synergy.com), has been retracted by agreement between the authors, the journal Editor in Chief, Takashi Tsuruo, and Blackwell Publishing. All authors wish to retract this paper because of the use of RGM-1 without the prior permission of the original establisher. Proton pump inhibitors have been used for treatment of acid-related gastroesophageal diseases and they act as potent inhibitors of gastric acid pump, H+/K+ -ATPase. Since cancer cells in vivo often exist in an ischemic microenvironment with a lower pH, maintenance of cellular pH is important for cell survival. In this study, we evaluated whether blocking of proton extrusion with proton pump inhibitors could inhibit the viability of gastric cancer cells. Treatment of human gastric cancer cells with proton pump inhibitors significantly attenuated cell viability in a time- and dose-dependent manner. The pro-apoptotic activity of proton pump inhibitors was mediated by release of cytochrome c and caspases activation. Gastric cancer cells showed the resistance to acidity of culture medium, which was related with a remarkable increase of extracellular signal-regulated protein kinase 1/2 (ERK1/2) phosphorylation in the acidic condition. This ERK1/2 phosphorylation was completely inhibited by pretreatment with proton pump inhibitors, suggesting that its inhibitory action on phosphorylation of ERK1/2 might contribute to the induction of apoptosis in gastric cancer cells. In conclusion, our results suggest novel therapeutic approaches for gastric cancer with proton pump inhibitors. (Cancer Sci 2008; 99: 185,185) [source]

Adiponectin inhibits the growth and peritoneal metastasis of gastric cancer through its specific membrane receptors AdipoR1 and AdipoR2

CANCER SCIENCE, Issue 7 2007
Makoto Ishikawa
Adiponectin, a circulating peptide hormone produced in adipose tissue, has been shown to be reduced in the plasma of patients with cancer, suggesting that this adipokine may be mechanically involved in the pathogenesis of adiposity-related carcinogenesis. In this study, we examined the expression of adiponectin receptors (AdipoR1 and AdipoR2) and assessed the function of adiponectin in gastric cancer. All of the six gastric cancer cell lines significantly expressed mRNA and protein of both receptors with variable levels. Addition of 30 µg/mL adiponectin potently induced apoptosis and inhibited the proliferation of AZ521 and HCG27. Down-regulation of either AdipoR1 or AdipoR2 by specific siRNA significantly suppressed the growth inhibitory effects of adiponectin in both cell lines. Moreover, a local injection of adiponectin markedly inhibited the growth of AZ521 inoculated subcutaneously in nude mice. Similarly, the continuous intraperitoneal infusion of adiponectin effectively suppressed the development of peritoneal metastasis of AZ521. Adiponectin negatively regulates the progression of gastric cancer cells possibly through both AdipoR1 and AdipoR2. Although adiponectin was already reported to have antiangiogenic effects, our results suggest that the antitumor effect of adiponectin was, at least partially, dependent on the direct effects on tumor cells. (Cancer Sci 2007; 98: 1120,1127) [source]

Hypermethylation of the TSLC1 Gene Promoter in Primary Gastric Cancers and Gastric Cancer Cell Lines

CANCER SCIENCE, Issue 8 2002
Teiichiro Honda
The TSLC1 (tumor suppressor in lung cancer,1) gene is a novel tumor suppressor gene on chromosomal region 11q23.2, and is frequently inactivated by concordant promoter hypermethylation and loss of heterozygosity (LOH) in non-small cell lung cancer (NSCLC). Because LOH on 11q has also been observed frequently in other human neoplasms including gastric cancer, we investigated the promoter methylation status of TSLC1 in 10 gastric cancer cell lines and 97 primary gastric cancers, as well as the corresponding non-cancerous gastric tissues, by bisulfite-SSCP analysis followed by direct sequencing. Allelic status of the TSLC1 gene was also investigated in these cell lines and primary gastric cancers. The TSLC1 promoter was methylated in two gastric cancer cell lines, KATO-III and ECC10, and in 15 out of 97 (16%) primary gastric cancers. It was not methylated in non-cancerous gastric tissues, suggesting that this hypermethylation is a cancer-specific alteration. KATO-III and ECC10 cells retained two alleles of TSLC1, both of which showed hypermethylation, associated with complete loss of gene expression. Most of the primary gastric cancers with promoter methylation also retained heterozygosity at the TSLC1 locus on 11q23.2. These data indicate that bi-allelic hypermethylation of the TSLC1 promoter and resulting gene silencing occur in a subset of primary gastric cancers. [source]

A case of gastric cancer with high pepsinogen II levels in both serum and ascites

DIGESTIVE ENDOSCOPY, Issue 1 2000
Manabu Muto
The first case of gastric cancer in which pepsinogen (PG) II levels were found to be extremely high not only in the serum but also in the ascites, with values of 603 ng/mL and 1910 ng/mL, respectively, is reported. Pepsinogen I and PG II are normally secreted into the gastric lumen and only 1% of the amount secreted enters the circulation. Although gastric cancer cells are found to produce PG II more often than PG I, elevated PG values in serum are extremely rare, and only one case has ever been reported. That patient had extremely high serum levels of PG I and PG II at the time of gastric cancer relapse. Pepsinogen has never been reported in the ascites, and thus nothing is known about the mechanism of entry into the ascites. In this case report, we postulate two mechanisms to explain the increased PG II in the ascites: (i) a high level of serum PG II infiltrated the ascites and caused elevation of PG II in the ascites; or (ii) disseminated cancer cells directly produced PG II and it elevated PG II levels in the ascites. [source]

Inhibition of PI3K/Akt partially leads to the inhibition of PrPC -induced drug resistance in gastric cancer cells

FEBS JOURNAL, Issue 3 2009
Jie Liang
Cellular prion protein (PrPC), a glycosyl-phosphatidylinositol-anchored membrane protein with unclear physiological function, was previous found to be upregulated in adriamycin (ADR)-resistant gastric carcinoma cell line SGC7901/ADR compared to its parental cell line SGC7901. Overexpression of PrPC in gastric cancer has certain effects on drug accumulation through upregulation of P-glycoprotein (P-gp), which is suggested to play an important role in determining the sensitivity of tumor cells to chemotherapy and is linked to activation of the phosphatidylinositol-3-kinase/Akt (PI3K/Akt) pathway. In the present study, we further investigate the role of the PI3K/Akt pathway in PrPC -induced multidrug-resistance (MDR) in gastric cancer. Immunohistochemistry and confocal microscope detection suggest a positive correlation between PrPC and phosphorylated Akt (p-Akt) expression in gastric cancer. Using established stable PrPC transfectant cell lines, we demonstrated that the level of p-Akt was increased in PrPC -transfected cells. Inhibition of PrPC expression by RNA interference resulted in decreased p-Akt expression. Inhibition of the PI3K/Akt pathway by one of its specific inhibitors, LY294002, or by Akt small interfering RNA (siRNA) resulted in decreased multidrug resistance of SGC7901 cells, partly through downregulation of P-gp induced by PrPC. Taken together, our results suggest that PrPC -induced MDR in gastric cancer is associated with activation of the PI3K/Akt pathway. Inhibition of PI3K/Akt by LY2940002 or Akt siRNA leads to inhibition of PrPC -induced drug resistance and P-gp upregulation in gastric cancer cells, indicating a possible novel mechanism by which PrPC regulates gastric cancer cell survival. [source]

The Effects of Cyclooxygenase2,ProstaglandinE2 Pathway on Helicobacter pylori -Induced Urokinase-Type Plasminogen Activator System in the Gastric Cancer Cells

Effect of H. pylori on the Expression of TRAIL, FasL and their Receptor Subtypes in Human Gastric Epithelial Cells and their Role in Apoptosis

HELICOBACTER, Issue 5 2004
Jan Hendrik Martin
ABSTRACT Background and Aims., In the human stomach expression of TNF-related apoptosis inducing ligand (TRAIL) and its receptors and the modulatory role of Helicobacter pylori are not well described. Therefore, we investigated the effect of H. pylori on the expression of TRAIL, FasL and their receptors (TRAIL-R1-R4, Fas) in gastric epithelial cells and examined their role in apoptosis. Materials and Methods., mRNA and protein expression of TRAIL, FasL and their receptors were analyzed in human gastric epithelial cells using RT-PCR, Western blot, and immunohistochemistry. Gastric epithelial cells were incubated with FasL, TRAIL and/or H. pylori, and effects on expression, cell viability and epithelial apoptosis were monitored. Apoptosis was analyzed by histone ELISA, DAPI staining and immunohistochemistry. Results., TRAIL, FasL and their receptor subtypes were expressed in human gastric mucosa, gastric epithelial cell primary cultures and gastric cancer cells. TRAIL, FasL and H. pylori caused a time- and concentration-dependent induction of DNA fragmentation in gastric cancer cells with synergistic effects. In addition, H. pylori caused a selective up-regulation of TRAIL, TRAIL-R1 and Fas mRNA and protein expression in gastric cancer cells. Conclusions., Next to FasL and Fas, TRAIL and all of its receptor subtypes are expressed in the human stomach and differentially modulated by H. pylori. TRAIL, FasL and H. pylori show complex interaction mediating apoptosis in human gastric epithelial cells. These findings might be important for the understanding of gastric epithelial cell kinetics in patients with H. pylori infection. [source]

Gastrin suppresses the interdependent expression of p16 and anion exchanger 1 favoring growth inhibition of gastric cancer cells

INTERNATIONAL JOURNAL OF CANCER, Issue 6 2010
Hua Tian
Abstract Our previous studies demonstrated that expression and interaction of p16 with anion exchanger 1 (AE1) in gastric cancer cells is correlated with progression and shorter survival of the cancer. In this article, the effects of gastrin on p16 and AE1 and its implication in prevention and treatment of gastric cancer were studied by molecular biology techniques, animal experiment and clinical analysis. The results showed that expression of p16 in human gastric body carcinoma was downregulated along with the progression of the cancer, suggesting the reverse correlations between gastrin and p16 in vivo. Further experiments indicated that gastrin suppressed the expression of p16 via the p16 promoter and thereafter resulted in the degradation of AE1 in gastric cancer cells. Silencing of AE1 or p16 significantly inhibited the proliferation of the cancer cells. Using a xenograft tumor model in nude mice, we showed that experimental systemic hypergastrinemia induced by the administration of omeprazole led to decreased expression of AE1 and p16 as well as to a marked growth inhibition of SGC7901 tumors. It is concluded that a moderate plasma gastrin level is beneficial to the growth inhibition of gastric cancer by suppressing the expression of AE1 and p16. This finding may have an important implication for the prevention and treatment of cancers arise in the gastric antrum. [source]

Phosphoglycerate kinase 1 a promoting enzyme for peritoneal dissemination in gastric cancer,

INTERNATIONAL JOURNAL OF CANCER, Issue 6 2010
Derek Zieker
Abstract Peritoneal carcinomatosis is a frequent finding in gastric cancer associated with a poor prognosis. The features that enable gastric tumors to disseminate are poorly understood until now. Previously, we showed elevated mRNA levels of phosphoglycerate kinase 1 (PGK1), an adenosine triphosphate-generating enzyme in the glycolytic pathway, the chemokine receptor 4 (CXCR4), the corresponding chemokine ligand 12 (CXCL12) and ,-catenin in specimens from gastric cancer patients with peritoneal carcinomatosis. In this study, the influence of PGK1 on CXCR4 and ,-catenin was assessed as well as the invasiveness of PGK1 overexpressing cancer cells. In this current study, we found that PGK1 regulates the expression of CXCR4 and ,-catenin at the mRNA and protein levels. On the other hand, CXCR4 regulates the expression of PGK1. Plasmid-mediated overexpression of PGK1 dramatically increased the invasiveness of gastric cancer cells. Interestingly, inhibition of CXCR4 in cells overexpressing PGK1 produced only a moderate reduction of invasiveness suggesting that, PGK1 itself has a critical role in tumor invasiveness. Immunohistochemistry in specimens from diffuse gastric cancer patients also revealed an overexpression of PGK1 in patients with development of peritoneal carcinomatosis. Therefore, PGK1 may be a crucial enzyme in peritoneal dissemination. Together these findings suggest that the enhanced expression of PGK1 and its signaling targets CXCR4 and ,-catenin in gastric cancer cells promote peritoneal carcinomatosis. Thus, PGK1 may serve as prognostic marker and/or be a potential therapeutic target to prevent dissemination of gastric carcinoma cells into the peritoneum. [source]

The dual EGFR/HER-2 tyrosine kinase inhibitor lapatinib sensitizes colon and gastric cancer cells to the irinotecan active metabolite SN-38

INTERNATIONAL JOURNAL OF CANCER, Issue 12 2009
Melissa J. LaBonte
Abstract Members of the human epidermal receptor (HER) family are frequently associated with aggressive disease and poor prognosis in multiple malignancies. Lapatinib is a dual tyrosine kinase inhibitor targeting the epidermal growth factor receptor (EGFR) and HER-2. This study evaluated the therapeutic potential of lapatinib, alone and in combination with SN-38, the active metabolite of irinotecan (CPT-11), in colon and gastric cancer cell lines. Concentration-dependent antiproliferative effects of both lapatinib and SN-38 were observed in all colon and gastric cancer cell lines tested but varied significantly between individual cell lines (lapatinib range 0.08,11.7 ,M; SN-38 range 3.6,256 nM). Lapatinib potently inhibited the growth of a HER-2 overexpressing gastric cancer cell line and demonstrated moderate activity in gastric and colon cancer cells with detectable HER-2 expression. The combination of lapatinib and SN-38 interacted synergistically to inhibit cell proliferation in all colon and gastric cancer cell lines tested. Cotreatment with lapatinib and SN-38 also resulted in enhanced cell cycle arrest and the induction of apoptosis with subsequent cellular pharmacokinetic analysis demonstrating that lapatinib promoted the increased intracellular accumulation and retention of SN-38 when compared to SN-38 treatment alone. Finally, the combination of lapatinib and CPT-11 demonstrated synergistic antitumor efficacy in the LoVo colon cancer mouse xenograft model with no apparent increase in toxicity compared to CPT-11 monotherapy. These results provide compelling preclinical rationale indicating lapatinib to be a potentially efficacious chemotherapeutic combination partner for irinotecan in the treatment of gastrointestinal carcinomas. © 2009 UICC [source]

Transforming properties of TC-1 in human breast cancer: Interaction with FGFR2 and ,-catenin signaling pathways

INTERNATIONAL JOURNAL OF CANCER, Issue 6 2007
Zeng-Quan Yang
Abstract Breast cancer development is associated with gene amplification and over expression that is believed to have a causative role in oncogenesis. Previous studies have demonstrated that over expression of TC-1(C8orf4) mRNA occurs in ,50% of breast cancer cell lines and primary tumor specimens. Here, we show that TC-1 has transforming properties in human mammary epithelial (HME) cells and its expression is mechanistically linked to FGFR signaling cascades. In vitro experiments demonstrate that TC-1 over expression mediates both anchorage-independent and growth factor-independent proliferation of HME cells. TC-1 was down regulated by the FGFR inhibitor PD173074 in the breast cancer cell line SUM-52 that also has an FGFR2 gene amplification and over expression. Furthermore, forced expression of FGFR2 in HME cells increased the level of expression of endogenous TC-1 mRNA. TC-1 has been implicated as a modulator of Wnt/,-catenin signaling in 293 cells and in gastric cancer cells. However, while we did find increased expression of a subset of ,-catenin target genes in TC-1 over expressing cells, we did not find an association of TC-1 with global expression of ,-catenin target genes in our cells. Taken together, our data suggest that TC-1 over expression is transforming and may link with the FGFR pathway in a subset of breast cancer. © 2007 Wiley-Liss, Inc. [source]

Selective cyclooxygenase-2 inhibitor downregulates the paracrine epithelial,mesenchymal interactions of growth in scirrhous gastric carcinoma

INTERNATIONAL JOURNAL OF CANCER, Issue 3 2007
Masakazu Yashiro
Abstract The importance of cancer-mesenchymal interactions in the aggressive behavior of scirrhous gastric cancer is supported by experimental and clinical evidences. We have previously reported that gastric fibroblasts secretion of keratinocyte growth factor (KGF) underline the remarkable proliferation of scirrhous gastric cancer cells. Cyclooxygenase-2 (COX-2) is not only expressed in cancer cells, but also in interstitial fibroblasts in gastric carcinoma. To clarify the mechanisms responsible for the antiproliferation effect of COX-2 inhibitors, effect of COX-2 inhibitor on the paracrine epithelial,mesenchymal interactions of growth was examined. Scirrhous gastric cancer cell line, OCUM-2M, gastric fibroblasts, NF-21, and COX-2 inhibitor, JTE-522, were used. Growth-interaction was examined by calculating the number of cancer cells or by measuring [3H] thymidine incorporation of cancer cells. Effect of JTE-522 on KGF expression from NF-21 cells and OCUM-2M cells was analyzed by ELISA and RT-PCR. The conditioned medium from gastric fibroblasts significantly stimulated the growth of scirrhous gastric cancer cells. JTE-522 at the concentrations of 10,5 and 10,6 M significantly decreased the growth-stimulating activity of gastric fibroblasts. JTE-522 reduced the expression of KGF mRNA and the production of KGF from gastric fibroblasts. Oral administration of JTE-522 significantly decreased the size of xenografted tumor coinoculated with OCUM-2M cells and NF-21 cells in nude mice. JTE-522 decreased COX-2 expression and Ki67 labeling index within the coinoculated tumor. These findings suggested that a selective COX-2 inhibitor, JTE-522, downregulates KGF production from gastric fibroblasts, resulting in the inhibition of paracrine epithelial,mesenchymal interactions of proliferation between scirrhous gastric cancer cells and gastric fibroblasts. © 2006 Wiley-Liss, Inc. [source]

Conjugated linoleic acid inhibits peritoneal metastasis in human gastrointestinal cancer cells

INTERNATIONAL JOURNAL OF CANCER, Issue 3 2006
Hiroki Kuniyasu
Abstract The effect of conjugated linoleic acid (CLA) on peritoneal metastasis was examined by in vitro treatment of cancer cells and mouse peritoneal metastasis models. First, cell growth of MKN28 human gastric cancer cells and Colo320 human colon cancer cells was suppressed by CLA in a dose-dependent manner with an increment in apoptosis. CLA significantly inhibited invasion into type IV collagen-coated membrane of MKN28 and Colo320 cells (p < 0.05). CLA-induced growth inhibition was recovered by the exposure to antisense S-oligodeoxynucleotide for peroxisome proliferator-activated receptor (PPAR)-, in both cell lines. BALB/c nu-nu mice were inoculated with MKN28 and Colo320 cells into their peritoneal cavity, and administrated with CLA intraperitoneally (weekly, 4 times). CLA treatment did not affect food intake or weight gain of mice. CLA treatment significantly decreased metastatic foci of both cells in the peritoneal cavity (p < 0.005). Survival rate in mice inoculated with MKN28 or Colo320 cells was significantly recovered by CLA treatment (p = 0.0025 and 0.0052, respectively). Protein production in MKN28 and Colo320 cells treated with CLA showed a decrease in epidermal growth factor receptor and transforming growth factor-, and an increase in Bax. These findings suggest that CLA inhibits metastasis of human gastric and colon cancer cells. © 2005 Wiley-Liss, Inc. [source]

Osteopontin promotes gastric cancer metastasis by augmenting cell survival and invasion through Akt-mediated HIF-1, up-regulation and MMP9 activation

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 8b 2009
Gang Song
Abstract Osteopontin (OPN) is a secreted, integrin-binding matrix phosphorylated glycoprotein. OPN has been shown to facilitate the progression and metastasis of malignancies and has prognostic value in several types of cancer, including gastric cancer. However, the functional mechanism of OPN mediated metastatic growth in gastric cancer remains unclear. Here, using multiple in vitro and in vivo models, we report that OPN strongly promoted the progression and metastasis of gastric cancer. Immunohistochemical staining revealed that OPN, matrix metalloproteinase (MMP)9 and hypoxia-inducible factor (HIF)-1, have statistically significant different expression patterns between well- and poorly differentiated tissue samples (P < 0.05). Correlations existed between OPN and MMP9, and between OPN and HIF-1, (r1= 0.872, p1 < 0.01 and r2= 0.878, p2 < 0.01). Furthermore, OPN dramatically increased colony formation and invasion of gastric cancer cells in vitro and promoted tumour growth and metastasis in vivo. In addition, OPN potently protected gastric cancer cells from serum depletion-induced apoptosis. Further study shows that OPN activated phosphoinositide 3-kinase/Akt survival pathway and up-regulated HIF-1,via binding to ,v,3 integrins in gastric cancer cells. Moreover, we found that OPN could activate MMP9 and up-regulate MMP2. Taken together, our results suggest that the survival-promoting function is crucial for OPN to promote the development of gastric cancer, and HIF-1, and MMP9 may play key roles during this process. Thus, targeting OPN and its related signalling network may develop an effective therapeutic approach for the management of gastric cancer. [source]

Mechanisms involved in hydroxycamptothecin-induced apoptosis of gastric cancer cells

JOURNAL OF DIGESTIVE DISEASES, Issue 1 2002
Shui Ping TU
OBJECTIVE: Hydroxycamptothecin (HCPT) is a unique antitumor drug that acts directly on topoisomerase I and inhibits its activity. However, the mechanism of HCPT-induced apoptosis is unclear. In the present study, the mechanism of HCPT-induced apoptosis in gastric cancer cells was investigated by detecting the expression of p53, c - myc, bcl-2, bcl-xl and bcl-xs genes in gastric cancer cells. METHODS: Apoptosis of gastric cancer cells (SGC-7901, MKN-45) was determined by terminal deoxyribonucleotidyl transferase-mediated dUTP, digoxigenin nick-end labeling (TUNEL) and flow cytometry. The mRNA and protein levels of the p53, c-myc, bcl-2, bcl-xl and bcl-xs genes were tested by reverse transcription,polymerase chain reaction analysis and immunocytochemical stain, respectively. RESULTS: Hydroxycamptothecin may induce apoptosis in different differentiated gastric cancer cells. The effect of HCPT-induced apoptosis on gastric cancer cells was dependent on the dose of HCPT used and the time of exposure to HCPT. Both SGC-7901 and MKN-45 cells manifested some morphological features of apoptosis after 12 h exposure to HCPT, including cell shrinkage, nuclear condensation, DNA fragmentation and formation of apoptotic bodies. Some typical subdiploid peaks before the G0/G1 phase were observed. The apoptotic rates induced by 10 ,g/mL HCPT in SGC-7901 and MKN-45 cells were 21.88 and 12.34%, respectively. The mRNA and protein levels of p53 and bcl-2 were downregulated after treatment with HCPT in SGC-7901 cells. However, the c-myc, bcl-xl and bcl-xs protein levels were unchanged in SGC-7901 cells. In MKN-45 cells, the mRNA and protein levels of p53 increased after treatment with HCPT, whereas the protein levels of bcl-2, c-myc, bcl-xl and bcl-xs remained unchanged. CONCLUSIONS: Our results indicate that HCPT-induced apoptosis in gastric cancer cells may be regulated through modulation of the expression of p53 and bcl-2 genes. [source]

Screening of gastric cancer cell sublines using the adhesion method

JOURNAL OF DIGESTIVE DISEASES, Issue 3 2001
Xiangrong Chen
OBJECTIVE: To screen subpopulations of gastric cancer cell lines with different malignant phenotypes. METHODS: Two subpopulations from the human gastric cancer cell line MKN-45 were separated by using the laminin adhesion method. One subpopulation was less invasive and non-metastatic, whereas the other was more invasive and metastatic. The relative invasiveness and migratory capacities of the two subgroups were observed by using the Boyden chamber and by inoculating the cells into nude mice. RESULTS: The two subgroups, the laminin-adherent cells (Lm+) and the laminin non-adherent cells (Lm,), were separated. During in vitro experiments, the Lm+ cells were more invasive and their migratory ability was greater relative to the Lm, cells. The rates of tumor formation after subcutaneous inoculation in nude mice and of lung tumor foci formation after tail vein inoculation were higher in Lm+ cells than those in Lm, cells. In vivo, Lm+ cells were found to have higher metastatic potential and to be more invasive. CONCLUSIONS: In vitro, the adhesion method is a simple and time-saving way to screen a particular phenotypic cell subpopulation with a high success rate. There are discrepancies in invasiveness and migratory ability between in vitro Lm+ and Lm, cells, which suggests that these properties of gastric cancer cells are closely related to their adhesiveness to the basement membrane and extracellular matrix. [source]

Expression and subcellular location of COX-2 in human gastric cancer cells

JOURNAL OF DIGESTIVE DISEASES, Issue 2 2001
Li Ling
OBJECTIVE: To detect the expression of cyclooxygenase (COX) in human gastric cancer cell lines and determine the subcellular location of its isoforms. METHODS: Immunohistochemistry, reverse transcription,polymerase chain reaction (RT-PCR), and laser scanning confocal microscopy (LSCM) were used to investigate the expression and distribution of COX. RESULTS: Positive staining for COX-2 and COX-1 protein was seen in human gastric cancer cell lines MKN45, SGC7901 and AGS. However, COX-2 staining was absent and COX-1 staining was weak in the MGC803 cell line, although COX-2 mRNA was present in all four cell lines. When compared with COX-1, COX-2 was more strongly expressed at both protein and mRNA levels in the gastric cancer cell lines, which was confirmed by double labeling and LSCM. A quantitative analysis of fluorescein intensity indicated that the pixel intensity peak of COX-2 had a gray scale value of 50,70, while COX-1 was only 10. The LSCM technique also revealed the presence of COX-2 in the cytoplasm and nuclear envelope and COX-1 in the cytoplasm only. CONCLUSIONS: In human gastric cancer cells, COX-2 is expressed at higher levels than COX-1 and the different distributions of the two isoforms suggest that their roles in cell function are distinct. [source]

Anti-cancer activity of anti-p185HER-2 ricin A chain immunotoxin on gastric cancer cells

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2010
Xin-Xin Zhou
Abstract Background and Aim:, Overexpression of the human epidermal growth factor receptor 2 (HER-2) protein has been detected in gastric cancer and has been associated with an unfavorable prognosis. We investigated the anti-cancer effects of anti-p185HER-2 ricin A chain (RTA) immunotoxin, alone or in combination with 5-flurouracil on SGC7901-HER-2+ cells. Methods:, SGC7901-HER-2+ cells were obtained by transfecting SGC7901 cells with HER-2-pcDNA3.1. Anti-p185HER-2 -RTA was prepared by chemical conjugation of anti-HER-2 monoclonal antibody (mAb) and RTA. The SGC7901-HER-2+ cells were incubated with RTA, anti-p185HER-2 -RTA, and/or 5-flurouracil. The effects of drugs on cells were evaluated by MTT assay and Annexin V-fluorescein isothiocyanate and propidium iodide double staining flow cytometry. The expression of caspase-3, caspase-9, cyclooxygenase-2, and nuclear factor-,B/p65 were assayed by western blot. SGC7901-HER-2+ cells were transplanted into BALB/c nude mice to produce solid tumors in an attempt to study the immunotoxin activity in vivo. Results:,In vitro, anti-p185HER-2 -RTA inhibited cell growth and induced apoptosis in SGC7901-HER-2+ cells. Anti-p185HER-2 -RTA enhanced caspase-3 and caspase-9 activity, while downregulating the expression of cyclooxygenase-2 and nuclear factor-,B/p65. Its combination with 5-flurouracil further inhibited the growth of SGC7901-HER-2+ cells. In vivo, our data showed that anti-p185HER-2 -RTA significantly inhibited the growth of SGC7901-HER-2+ cells-transplanted tumors. Conclusions:, Anti-p185HER-2 -RTA inhibits the growth of SGC7901-HER-2+ cells. The effect may be related to the activation of caspase-3 and caspase-9 and inhibition of cyclooxygenase-2 and nuclear factor-,B/p65. Anti-p185HER-2 -RTA plus 5-FU enhance anti-cancer activity, suggesting useful clues for further study for the treatment of HER-2 positive gastric cancers. [source]

Molecular basis of therapeutic approaches to gastric cancer

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 1 2009
Kaichun Wu
Abstract Gastric cancer is the top lethal cancer in Asia. As the majority of cases present with advanced disease, conventional therapies (surgery, chemotherapy, and radiotherapy) have limited efficacy to reduce mortality. Emerging modalities provide promise to combat this malignancy. Target-protein-based cancer therapy has become available in clinical practice. Numerous molecules have been shown potential to target specific pathways for tumor cell growth. Cyclooxygenase-2 (COX-2) is overexpressed in and correlated with gastric cancer, and knockdown of COX-2 or administration of COX-2 inhibitors suppresses tumor formation in models of gastric cancer. Induction of apoptosis, reduction of angiogenesis, and blocking of potassium ion channels may present new mechanisms of COX-2 inhibition. Runt-related transcription factor 3 (RUNX3) is a candidate tumor suppressor gene whose deficiency is causally related to gastric cancer. RUNX3 is downregulated in metastatic gastric cancer. RUNX3 activation inhibits angiogenesis in xenograft tumors in nude mice. Tumor microenvironment modulation also provides a powerful tool to inhibit cancer development and progress; details of the potential roles of angiopoietins are discussed in this review. Osteopontin is a secreted protein involved in stress response, inflammation, wound healing, and immune response. Inhibition of osteopontin by RNA interfering technique suppressed tumorigenesis as well as angiogenesis in gastric cancer. Immunotherapy remains another important choice of adjuvant therapy for cancer. A tumor-specific antigen MG7-Ag has been identified with great potential for inducing immune response in gastric cancer. Using HLA-A-matched allogeneic gastric cancer cells to induce tumor-specific cytotoxic T lymphocytes appeared to be an alternative option of immunotherapy for gastric cancer. [source]

Gene expression of AGS cells stimulated with released proteins by Helicobacter pylori

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2008
Nayoung Kim
Abstract Background and Aim:, Interactions between released proteins by Helicobacter pylori (H. pylori) and the cells of gastric epithelium to which it adheres may contribute to gastric inflammation and epithelial damage. The present study was performed to evaluate the gene expression of AGS gastric cancer cells stimulated with released proteins by H. pylori. Methods:, Gene expression of AGS cells to the stimulation by H. pylori -released proteins (G27 strain) were monitored using oligonucleotide microarrays. Results:, Eighty-eight genes (0.88%) and eight genes (0.08%) were up- or downregulated, respectively, by treating AGS cells with H. pylori -released proteins but not by H. pylori adhesion after 12 h of coculture. Out of the selected 40 up- and five downregulated genes, 29 upregulated genes classified as general RNA polymerase II transcription factor activity (GTF2B, PPARGC1A), SH3/SH2 adaptor activity (CRKL), transferase activity (ACLY, CRKL, PIGC, PLK4), and oxidoreductase activity (IDH1) were confirmed to be upregulated by released proteins and not by H. pylori adhesion by real-time reverse transcription,polymerase chain reaction. When the concentrated H. pylori -cultured supernatant prepared by our protocol was treated by boiling, the upregulations of 26 of these 29 genes (89.7%) except for CD160, ZNF268, and PSAT1 disappeared. This confirmed that most of these upregulations were caused by released proteins. Conclusion:, Host genes involving transcription, signaling and stress are significantly modulated by the proteins released by H. pylori. This might strengthen the gastroduodenal pathogenesis induced by H. pylori. [source]

Increased wild-type p53-induced phosphatase 1 (Wip1 or PPM1D) expression correlated with downregulation of checkpoint kinase 2 in human gastric carcinoma

PATHOLOGY INTERNATIONAL, Issue 9 2007
Takeichi Fuku
Phosphorylation of checkpoint kinase 2 (Chk2) at Thr68 (pChk2) induced by DNA double-strand breaks is required for inhibition of cell cycle progression in the G2 phase. The purpose of the present paper was to investigate the expression of wild-type p53-induced phosphatase 1 (Wip1 or PPM1D), a negative regulator of Chk2, to better understand its role in human gastric cancer. In non-neoplastic gastric mucosa, most epithelial cells exhibited Wip1-positive and pChk2-negative immunoreactivity, whereas an inverse pattern of protein expression was detected at the surface of the foveolar epithelium. In tumor tissues, 74% of 53 gastric cancers had intense Wip1 immunoreactivity and close correlation with both tumor size (P = 0.0497) and Chk2 dephosphorylation (P = 0.0213). In MKN-74 gastric cancer cells, ionizing radiation (IR)-induced Wip1 upregulation was detected at protein levels, but the Chk2-mediated cell cycle regulatory mechanism was disrupted. In addition, protease inhibitor Z-Leu-Leu-Leu (ZLLL) effectively upregulated Wip1 levels in the presence or absence of IR, suggesting that Wip1 expression can be modulated post-transcriptionally. Understanding the Wip1-mediated signaling pathway in gastric cancer may provide useful information for the development of new chemo- and radiotherapies. [source]

Coptis japonica root extract induces apoptosis through caspase3 activation in SNU-668 human gastric cancer cells

PHYTOTHERAPY RESEARCH, Issue 3 2005
H. J. Park
Abstract Apoptosis-modulating approaches offer an attractive opportunity for therapeutic use for many tumors. We investigated the effects of the roots of Coptis japonica var. dissecta (Ranunculaceae) on human gastric cancer cells, SNU-668. The cytotoxicity of Coptis japonica at 100 µg[sol ]ml (methanol extract) by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was 13.89 ± 1.91% of control value. Considering the features by 4,6-diamidino-2-phenylindole (DAPI) staining and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, it was confirmed that the death of SNU-668 cells was due to apoptosis. In the apoptosis-regulating genes, BCL2 expression was diminished out, whereas BAX and CASP3 expressions were increased, compared with control. Furthermore, the activity of caspase3 was significantly increased by Coptis japonica treatment. These results suggest that Coptis japonica could induce apoptotic anticancer effect through caspase3 activation on SNU-668 human gastric cancer cells. Copyright © 2005 John Wiley & Sons, Ltd. [source]

Identification and Expression Analysis of a Novel CW-Type Zinc Finger Protein MORC2 in Cancer Cells

THE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 6 2010
Gui-Ling Wang
Abstract Microrchidia2 (MORC2) is a member of the MORC protein family that is localized to both the nucleus and cytoplasm when transiently expressed in gastric cancer cells. We identified and analyzed the functional domains of MORC2, which has specific unique structural characteristics compared to the other MORC proteins. Our data showed that nuclear localization signals (NLS) of MORC2 was mainly dependent on the NLS amino acids (aa) 657,781 and cytoplasmic localization of MORC2 was attributed to the nuclear export signal (NES) aa 481,657. Moreover, the NLS appears to predominate over the NES in the localization of full-length human MORC2 indicating that MORC2 is localized mainly in the nucleus. Our results also demonstrated that the NLS (aa 657,781) and proline-rich domain within MORC2 C-terminus were required for the transcriptional repressive role in cancer cells. Anat Rec, 2010. © 2010 Wiley-Liss, Inc. [source]

Glycogen synthase kinase-3, does not correlate with the expression and activity of ,-catenin in gastric cancer

APMIS, Issue 10 2010
YU-JIN CHO
Cho Y-J, Yoon J, Ko Y-S, Kim S-Y, Cho S-J, Kim W-H, Park J-W, Youn H-D, Kim J-H, Lee B-L. Glycogen synthase kinase-3, does not correlate with the expression and activity of ,-catenin in gastric cancer. APMIS 2010; 118: 782,90. The regulation of ,-catenin activation by glycogen synthase kinase-3, (GSK-3,) in cancer has been shown to be cell type-specific. This study was performed to investigate the relationship between activated GSK-3, (phosphorylated at Tyr216) and ,-catenin in gastric cancer. Immunohistochemical tissue array analysis of 278 human gastric carcinoma specimens showed positive immunoreactivity for activated GSK-3, in 44% of the samples, whereas membranous ,-catenin and nuclear ,-catenin were observed in 19% and 20% of the samples, respectively. However, GSK-3, activation was not correlated with the expression of either membranous ,-catenin or nuclear ,-catenin. Moreover, SNU gastric cancer cell lines over-expressing kinase dead GSK-3, and the same cells treated with a GSK-3, inhibitor showed that GSK-3, inhibition did not alter either the protein expression or transcriptional activity of ,-catenin. In addition, GSK-3, activation was positively correlated with the expressions of anti-adenomatous polyposis coli (p = 0.002), p16 (p < 0.001), p21 (p < 0.001), p27 (p = 0.001), and p53 (p = 0.013). On the other hand, the nuclear expression of ,-catenin was positively correlated with those of Bcl-2 (p = 0.025) and cyclin D1 (p = 0.043), but these expressions were not correlated with GSK-3, activation. Thus, the GSK-3, pathway seems to function in gastric cancer cells without involving the ,-catenin pathway. [source]

Loss of caspase-2, -6 and -7 expression in gastric cancers,

APMIS, Issue 6 2004
NAM JIN YOO
Caspases play an essential role during apoptotic cell death, and alterations of caspases are known to contribute to human cancer development. In the current study, we analyzed the expression of caspase-2, -6 and -7 in 120 gastric carcinomas by immunohistochemistry using a tissue microarray approach. Caspase-2, -6 and -7 were expressed in 42 (35%), 63 (53%) and 39 (33%) of the gastric cancers, respectively. By contrast, the surface mucous cells and mucosal glandular cells in the normal gastric mucosa showed strong immunoreactivity for caspase-2, -6 and -7. Taken together, these results indicate that caspase-2, -6 and -7 expression in gastric cancer cells is decreased compared to in normal gastric mucosal cells, and suggest that loss of caspase-2, -6 and -7 expression might be involved in the mechanisms of gastric cancer development. [source]

DNA methylation of interferon regulatory factors in gastric cancer and noncancerous gastric mucosae

CANCER SCIENCE, Issue 7 2010
Masaki Yamashita
Interferon regulatory factors (IRFs) are transcription factors known to play key roles in innate and adaptive immune responses, cell growth, apoptosis, and development. Their function in tumorigenesis of gastric cancer remains to be determined, however. In the present study, therefore, we examined epigenetic inactivation of IRF1,9 in a panel of gastric cancer cell lines. We found that expression of IRF4, IRF5, and IRF8 was frequently suppressed in gastric cancer cell lines; that methylation of the three genes correlated with their silencing; and that treating the cells with the demethylating agent 5-aza-2,-deoxycytidine (DAC) restored their expression. Expression of IRF5 in cancer cells was enhanced by the combination of DAC treatment and adenoviral vector-mediated expression of p53, p63, or p73. Interferon-,-induced expression of IRF8 was also enhanced by DAC. Moreover, treating gastric cancer cells with DAC enhanced the suppressive effects of interferon-,, interferon-,, and interferon-, on cell growth. Among a cohort of 455 gastric cancer and noncancerous gastric tissue samples, methylation of IRF4 was frequently observed in both gastric cancer specimens and noncancerous specimens of gastric mucosa from patients with multiple gastric cancers, which suggests IRF4 methylation could be a useful molecular marker for diagnosing recurrence of gastric cancers. Our findings indicate that epigenetic IRF inactivation plays a key role in tumorigenesis of gastric cancer, and that inhibition of DNA methylation may restore the antitumor activity of interferons through up-regulation of IRFs. (Cancer Sci 2010) [source]