title: Anti-HBV drugs suppress the growth of HBV-related hepatoma cells via down-regulation of hepatitis B virus X protein.
abstract: Chronic infection of hepatitis B virus (HBV) is closely associated with the development of hepatocellular carcinoma (HCC). Meta-analyses show that adjuvant anti-HBV therapy is effective for HBV-related HCC patients in clinical. However, the significance that anti-HBV drugs depress HCC is poorly understood. Here, we investigated the effects of telbivudine (LdT), entecavir (ETV) and interferon-α2b (IFN-α2b) on HBV-related HCC. Our data showed that the treatment with the drugs significantly suppressed the growth of HBV-expressing hepatoma cells in vitro and in vivo, but failed to work in HBV-free liver cells. We present the hypothesis that HBx may be involved in the event. As expected, we observed that the expression of HBx was down-regulated by the agents. Meanwhile, the expression of HBx downstream factors was significantly down-regulated. Interestingly, LdT, ETV and IFN-α2b lost the anti-proliferation effects on HBV-related hepatoma cells when the cells were treated with HBx siRNA. Moreover, combination of those drugs enhanced the anti-proliferation effects. In conclusion, LdT, ETV and IFN-α2b suppress the growth of HBV-related HCC through down-regulation of HBx. Our finding provides new insights into the mechanisms of anti-HBV drugs in HCC therapy.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin, 300071, China.
authors.forename: Shuqin
authors.initials: S
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin, 300071, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin, 300071, China.
authors.forename: Man
authors.initials: M
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin, 300071, China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin, 300071, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Bu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin, 300071, China.
authors.forename: Qiulei
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin, 300071, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin, 300071, China. Electronic address: yelihong@nankai.edu.cn.
authors.forename: Lihong
authors.initials: L
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin, 300071, China. Electronic address: zhangxd@nankai.edu.cn.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D049109:Cell Proliferation / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects; D004279:DNA, Viral / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004359:Drug Therapy, Combination; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D056945:Hep G2 Cells; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000378:metabolism; D006513:Hepatitis B e Antigens / Q000235:genetics / Q000378:metabolism; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008822:Mice, Transgenic; D034622:RNA Interference; D011994:Recombinant Proteins / Q000494:pharmacology; D000077712:Telbivudine; D013936:Thymidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*; D014162:Transfection; D047368:Tumor Burden / Q000187:drug effects; D054334:Viral Regulatory and Accessory Proteins; D014779:Virus Replication / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D000077712:Telbivudine; C413685:entecavir; D006147:Guanine; D013936:Thymidine
keywords: ETV; HBx; HCC; IFN-α2b; LdT