抗HBV药物通过下调乙型肝炎病毒X蛋白抑制HBV相关肝细胞瘤细

StephenW

Cancer Lett. 2017 Feb 9. pii: S0304-3835(17)30103-9. doi: 10.1016/j.canlet.2017.02.003. [Epub ahead of print]
Anti-HBV Drugs Suppress the Growth of HBV-related Hepatoma Cells via Down-regulation of Hepatitis B Virus X Protein.Zhang S1, Gao S1, Zhao M1, Liu Y1, Bu Y1, Jiang Q1, Zhao Q1, Ye L2, Zhang X3.
Author information

• 1State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, China.
• 2State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, China. Electronic address: [email protected].
• 3State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, China. Electronic address: [email protected].
  

AbstractChronic 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.

Copyright © 2017 Elsevier B.V. All rights reserved.

KEYWORDS: ETV; HBx; HCC; IFN-α2b; LdT

PMID:28192212DOI:10.1016/j.canlet.2017.02.003

StephenW

癌症。 2017 Feb。9i：S0304-3835（17）30103-9。 doi：10.1016 / j.canlet.2017.02.003。 [印刷前电子版]
抗HBV药物通过下调乙型肝炎病毒X蛋白抑制HBV相关肝细胞瘤细胞的生长。
Zhang S1，Gao S1，Zhao M1，Liu Y1，Bu Y1，Jiang Q1，Zhao Q1，Ye L2，Zhang X3。
作者信息

    1南开大学生命科学学院肿瘤研究系药物化学生物学国家重点实验室，天津300071。
    2南开大学生命科学学院生物化学系药物化学生物学国家重点实验室，天津300071。电子地址：[email protected]。
    南开大学生命科学学院肿瘤研究系药物化学生物学国家重点实验室，天津300071。电子地址：[email protected]。

抽象

乙型肝炎病毒（HBV）的慢性感染与肝细胞癌（HCC）的发展密切相关。 Meta分析显示，辅助抗HBV治疗对HBV相关HCC患者临床有效。然而，抗HBV药物抑制HCC的意义了解甚少。在这里，我们调查了telbivudine（LdT），恩替卡韦（ETV）和干扰素-α2b（干扰素-α2b）对HBV相关肝癌的影响。我们的数据表明，用药物的治疗显着抑制表达HBV的肝癌细胞在体外和体内的生长，但不能在无HBV的肝细胞中工作。我们提出HBx可能参与事件的假说。如预期的，我们观察到HBx的表达被试剂下调。同时，HBx下游因子的表达显着下调。有趣的是，当细胞用HBx siRNA处理时，LdT，ETV和IFN-α2b丧失对HBV相关肝癌细胞的抗增殖作用。此外，这些药物的组合增强了抗增殖作用。总之，LdT，ETV和IFN-α2b通过下调HBx抑制HBV相关HCC的生长。我们的研究结果提供了新的见解的抗HBV药物在HCC治疗的机制。

版权所有©2017 Elsevier B.V.保留所有权利。
关键词：

ETV; HBx; HCC; IFN-α2b; LdT

PMID：
    28192212
DOI：
    10.1016 / j.canlet.2017.02.003