Anti-HBV drugs suppress the growth of HBV-related hepatoma cells via down-regulation of hepatitis B virus X protein
Anti-HBV drugs suppress the growth of HBV-related hepatoma cells via down-regulation of hepatitis B virus X protein
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抗HBV药物通过下调乙型肝炎病毒X蛋白抑制HBV相关肝癌细胞的生长
DOI：
10.1016/j.canlet.2017.02.003
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发表时间：
2017-04-28
期刊：
影响因子：
9.7
通讯作者：
Zhang, Xiaodong
中科院分区：
文献类型：
--
作者：
Zhang, Shuqin;Gao, Shan;Zhang, Xiaodong
乙型肝炎病毒（HBV）的慢性感染与肝细胞癌（HCC）的发生密切相关。 Meta分析显示，临床上辅助抗HBV治疗对HBV相关HCC患者有效。然而，人们对抗乙型肝炎药物抑制肝癌的重要性知之甚少。在这里，我们研究了替比夫定 (LdT)、恩替卡韦 (ETV) 和干扰素-α 2b (IFN-α 2b) 对 HBV 相关 HCC 的影响。我们的数据表明，药物治疗在体外和体内显着抑制表达 HBV 的肝癌细胞的生长，但对不含 HBV 的肝细胞不起作用。我们提出 HBx 可能参与该事件的假设。正如预期的那样，我们观察到 HBx 的表达被药物下调。同时，HBx下游因子的表达显着下调。有趣的是，当用 HBx siRNA 处理细胞时，LdT、ETV 和 IFN-α 2b 失去了对 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-α 2b 通过下调 HBx 抑制 HBV 相关 HCC 的生长。我们的发现为抗乙型肝炎药物在肝癌治疗中的作用机制提供了新的见解。 (C) 2017 Elsevier B.V. 保留所有权利。
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-alpha 2b (IFN-alpha 2b) 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-alpha 2b 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-alpha 2b 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. (C) 2017 Elsevier B.V. All rights reserved.