Human Hepatocellular Carcinoma Cells (human + hepatocellular_carcinoma_cell)

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Terms modified by Human Hepatocellular Carcinoma Cells

  • human hepatocellular carcinoma cell line

  • Selected Abstracts

    MicroRNA-195 suppresses tumorigenicity and regulates G1/S transition of human hepatocellular carcinoma cells,

    HEPATOLOGY, Issue 1 2009
    Teng Xu
    Growing evidence indicates that deregulation of microRNAs (miRNAs) contributes to tumorigenesis. Down-regulation of miR-195 has been observed in various types of cancers. However, the biological function of miR-195 is still largely unknown. In this study we aimed to elucidate the pathophysiologic role of miR-195. Our results showed that miR-195 expression was significantly reduced in as high as 85.7% of hepatocellular carcinoma (HCC) tissues and in all of the five HCC cell lines examined. Moreover, introduction of miR-195 dramatically suppressed the ability of HCC and colorectal carcinoma cells to form colonies in vitro and to develop tumors in nude mice. Furthermore, ectopic expression of miR-195 blocked G1/S transition, whereas inhibition of miR-195 promoted cell cycle progression. Subsequent investigation characterized multiple G1/S transition-related molecules, including cyclin D1, CDK6, and E2F3, as direct targets of miR-195. Silencing of cyclin D1, CDK6, or E2F3 phenocopied the effect of miR-195, whereas overexpression of these proteins attenuated miR-195-induced G1 arrest. In addition, miR-195 significantly repressed the phosphorylation of Rb as well as the transactivation of downstream target genes of E2F. These results imply that miR-195 may block the G1/S transition by repressing Rb-E2F signaling through targeting multiple molecules, including cyclin D1, CDK6, and E2F3. Conclusion: Our data highlight an important role of miR-195 in cell cycle control and in the molecular etiology of HCC, and implicate the potential application of miR-195 in cancer therapy. (HEPATOLOGY 2009.) [source]

    Mechanisms of cell death induced by suicide genes encoding purine nucleoside phosphorylase and thymidine kinase in human hepatocellular carcinoma cells in vitro

    HEPATOLOGY, Issue 3 2001
    Tim U. Krohne
    For gene therapy of hepatocellular carcinoma (HCC), the Escherichia coli purine nucleoside phosphorylase (PNP)/fludarabine suicide gene system may be more useful than the herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) system as a result of a stronger bystander effect. To analyze the molecular mechanisms involved in PNP/fludarabine-mediated cell death in human HCC cells in comparison with HSV-tk/GCV, we transduced human HCC cells of the cell lines, HepG2 and Hep3B, with PNP or HSV-tk using adenoviral vectors, followed by prodrug incubation. Both systems predominantly induced apoptosis in HepG2 and Hep3B cells. PNP/fludarabine induced strong p53 accumulation and a more rapid onset of apoptosis in p53-positive HepG2 cells as compared with p53-negative Hep3B cells, but efficiency of tumor cell killing was similar in both cell lines. In contrast, HSV-tk/GCV,induced apoptosis was reduced in p53-negative Hep3B cells as compared with p53-positive HepG2 cells. HSV-tk/GCV, but not PNP/fludarabine, caused up-regulation of Fas in p53-positive HepG2 cells and of Fas ligand (FasL) in both HCC cell lines. These results demonstrate cell line,specific differences in response to treatment with PNP/fludarabine and HSV-tk/GCV, respectively, and indicate that PNP/fludarabine may be superior to HSV-tk/GCV for the treatment of human HCC because of its independence from p53 and the Fas/FasL system. (HEPATOLOGY 2001;34:511-518.) [source]

    Interferon alpha receptors are important for antiproliferative effect of interferon-, against human hepatocellular carcinoma cells

    Bazarragchaa Damdinsuren
    Aim:, Interferon (IFN)-, is a promising drug for the prevention and treatment of hepatocellular carcinoma (HCC). We reported that responders to IFN-,/5-fluorouracil combination therapy expressed higher IFN alpha receptor (IFNAR)2 in tumor. Herein we studied involvement of IFNARs in response to IFN-, in HCC cells. Methods:, IFN-, sensitivity and expression of IFNARs were studied in six HCC cell lines (HuH7, PLC/PRF/5, HLE, HLF, HepG2, Hep3B) using growth-inhibitory and RT-PCR, Western blot assays. Short interfering RNAs (SiRNAs) against IFNAR1 and 2 were used to analyze the role of the IFNARs in IFN-,'s effect and signal transduction. Results:, The expressions of IFNAR1 and 2c mRNAs were higher in PLC/PRF/5 cells than those in other cell lines, and PLC/PRF/5 cells expressed abundant IFNAR2c on their cell membrane. When we examined the sensitivity of the HCC cell lines to the growth-inhibitory effect of IFN-,, PLC/PRF/5 exhibited a significant response, while the other cells were much more resistant. Knockdown of either IFNAR1 or 2 using siRNAs suppressed the IFN-,'s signal transduction (2.5-fold), and decreased the growth-inhibitory effect (down by 69.9% and 67.3%). Conclusion:, The results suggest that the expression of IFNAR1 and IFNAR2c independently are important for the antiproliferative effect of IFN-, in HCC cells. [source]

    Upregulation of miR-23a,27a,24 decreases transforming growth factor-beta-induced tumor-suppressive activities in human hepatocellular carcinoma cells

    Shenglin Huang
    Abstract Transforming growth factor-beta (TGF-beta) plays a dual and complex role in human cancer. In this report, we observe a specific set of MicroRNAs (miRNAs) changed in response to TGF-beta in human hepatocellular carcinoma (HCC) cells by miRNA microarray screening. A cluster of miRNA, miR-23a,27a,24, is induced in an early stage by TGF-beta in Huh-7 cells. Knockdown of Smad4, Smad2 or Smad3 expression by RNA interference can attenuate the response of miR-23a,27a,24 to TGF-beta addition, indicating that this induction is dependent on Smad pathway. We also explore that miR-23a,27a,24 can function as an antiapoptotic and proliferation-promoting factor in liver cancer cells. In addition, expression of this miRNA cluster is found to be remarkably upregulated in HCC tissues versus normal liver tissues. These findings suggest a novel, alternative mechanism through which TGF-beta could induce specific miRNA expression to escape from tumor-suppressive response in HCC cells. © 2008 Wiley-Liss, Inc. [source]

    Basal replication of hepatitis C virus in nude mice harboring human tumor

    Patrick Labonté
    Abstract Hepatitis C virus (HCV) can infect and propagate in humans and chimpanzees. Whereas the chimpanzee has been used as an animal model for infection, ethical considerations, conservation, and the prohibitively high cost preclude progress for experimental research on the biology of the virus. The development of a small animal model for HCV infection is thus desirable to facilitate studies on the infectious cycle of the virus and for the evaluation of drugs for the treatment of HCV infections in humans. As an alternative to the chimpanzee model, we have established a model based on ex vivo infection of orthotopically-implanted human hepatocellular carcinoma cells (HCC) in athymic nude mice. The results show that up to 42 days post-infection, HCV RNA was present in the tumor cells as well as in the liver and serum of infected mice. Furthermore, a direct correlation between size of the tumor and the presence of HCV RNA in the liver was observed, which is concordant with the finding that HCV RNA was detectable only in mice harboring human tumor. Immunohistochemistry analysis of infected liver specimens showed cells expressing the HCV encoded NS5B protein. A few mice developed a humoral response against the nonstructural viral proteins, providing further evidence for expression of these proteins during viral infection. In summary, these results suggest that mice harboring orthotopic tumors support a basal level of HCV replication in vivo. J. Med. Virol. 66:312-319, 2002. © 2002 Wiley-Liss, Inc. [source]

    Involvement of p38 mitogen-activated protein kinase pathway in honokiol-induced apoptosis in a human hepatoma cell line (hepG2)

    LIVER INTERNATIONAL, Issue 10 2008
    Junfang Deng
    Abstract Background: Honokiol has been known to have antitumour activity. This study was conducted to evaluate the antiproliferative potential of honokiol against the hepG2 heptocellular cell line and its mechanism of action. Methods: hepG2 cells were treated with honokiol of 0,40 ,g/ml concentration. The cytotoxic effect of honokiol was determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptosis was evaluated by flow cytometry. Western blots were used to analyse the expression of various proteins (procaspase-9, procaspase-3, cleaved caspase-3, cytochrome c, Bcl-2, Bax, Bad, Bcl-XL and p38). Results: Honokiol induced apoptosis with a decreased expression of procaspase-3 and -9 and an increased expression of active caspase-3. Exposure of hepG2 cells to honokiol resulted in the downregulation of Bcl-XL and Bcl-2 expression and the release of mitochondrial cytochrome c to the cytosol. In addition, honokiol activated the p38 mitogen-activated protein kinase (MAPK) pathway, and the inhibition of this pathway by SB203580 reduced honokiol-induced apoptosis and activation of caspase-3. Conclusion: Honokiol induces apoptosis of hepG2 human hepatocellular carcinoma cells through activation of the p38 MAPK pathway, and, in turn, activation of caspase-3. [source]

    The hepatoprotective effects of Limonium sinense against carbon tetrachloride and , -D-galactosamine intoxication in rats

    Shang-Shing Chaung
    Abstract In the present study, the hepatoprotective action of Limonium sinense (Plumbaginaceae) was evident after carbon tetrachloride (CCl4) and , -D-galactosamine (D-GalN), respectively, challenge in rats. The plant materials were divided into two parts: (1) the roots extracted with water (WRE) and (2) the leaves extracted with methanol and fractionated with chloroform (CLE). Both WRE and CLE were extremely ,avonoid-enriched extracts. In an CCl4 -induced acute liver damage study, pretreatment with WRE at 300 mg/kg i.p. and CLE at 100 mg/kg i.p. signi,cantly reduced the amino-transaminases levels of SGOT (p < 0.01) and SGPT (p < 0.01) previously increased by CCl4 intoxication. In D-GalN-induced acute liver damage study, administration of WRE (300 and 500 mg/kg) or CLE (100 mg/kg) p.o. also signi,cantly reduced the SGOT (p < 0.01) and SGPT (p < 0.01) levels previously increased by D-GalN intoxication. Furthermore, the serum triglyceride level was increased after pretreatment with WRE or CLE previously reduced by D-GalN intoxication. All of the liver function pro,les were con,rmed to have improvement of liver lesion in histopathological obsvervation. In an acute toxicity test on ICR mice, the LD50 of WRE was 777.6 mg/kg i.p. An in vitro study showed that CLE possessed a more potent cytotoxicity to human hepatocellular carcinoma cells (Hep3B) (EC50 = 43.1 µg/mL) than the other organic fractions, which were fractionated from methanol extracts of the leaves of L. sinense. The present results conclude that L. sinense possesses a hepatoprotective ef,cacy, and is relatively safe in rats. Copyright © 2003 John Wiley & Sons, Ltd. [source]

    (,)-Epigallocatechin gallate suppresses the growth of human hepatocellular carcinoma cells by inhibiting activation of the vascular endothelial growth factor,vascular endothelial growth factor receptor axis

    CANCER SCIENCE, Issue 10 2009
    Yohei Shirakami
    The receptor tyrosine kinase vascular endothelial growth factor (VEGF) receptor (VEGFR) plays an important role in tumor angiogenesis of hepatocellular carcinoma (HCC). (,)-Epigallocatechin gallate (EGCG), the major biologically active component of green tea, inhibits growth in a variety of human cancer cells by inhibiting the activation of several types of receptor tyrosine kinases. In this study, we examined the effects of EGCG on the activity of the VEGF,VEGFR axis in human HCC cells. The levels of total and phosphorylated (i.e. activated) form of VEGFR-2 protein (p-VEGFR-2) were observed to increase in a series of human HCC cell lines in comparison to the Hc normal human hepatocytes. EGCG preferentially inhibited the growth of HuH7 HCC cells, which express constitutive activation of the VEGF,VEGFR axis, in comparison to Hc cells. Treatment of HuH7 cells with EGCG caused a time- and dose-dependent decrease in the expression of VEGFR-2 and p-VEGFR-2 proteins. The production of VEGF from HuH7 cells was reduced by treatment with EGCG. Drinking of EGCG significantly inhibited the growth of HuH7 xenografts in nude mice and this was associated with inhibition of the activation of VEGFR-2 and its related downstream signaling molecules, including ERK and Akt. EGCG drinking also decreased the expression of Bcl-xL protein and VEGF mRNA in the xenografts. These findings suggest that EGCG can exert, at least in part, its growth-inhibitive effect on HCC cells by inhibiting the VEGF,VEGFR axis. EGCG might therefore be useful in the treatment of HCC. (Cancer Sci 2009; 100: 1957,1962) [source]