Metformin inhibits hepatitis B virus protein production and replication in human hepatoma cells
Metformin inhibits hepatitis B virus protein production and replication in human hepatoma cells
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二甲双胍抑制人肝癌细胞中乙型肝炎病毒蛋白的产生和复制
DOI：
10.1111/jvh.12187
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发表时间：
2014-08
影响因子：
2.5
通讯作者：
Jiming Zhang
中科院分区：
文献类型：
--
作者：
Yongmei Zhang;Mengji Lu;Guoqing Zang;Jiming Zhang
乙肝病毒表面抗原在维持机体耐受性方面起着重要作用，可能会干扰宿主的先天免疫和获得性免疫反应，因此，降低乙肝病毒感染者体内的乙肝表面抗原载量的治疗策略成为一个既有吸引力又有挑战性的课题。二甲双胍可调节肝脏代谢，而后者与乙肝病毒感染有相互作用。我们推测，二甲双胍可以影响乙肝表面抗原的表达和乙肝病毒的复制，当与现有的抗病毒药物联合使用时，可能会产生协同作用。在我们的研究中，观察到二甲双胍对乙肝表面抗原的产生有显著的抑制作用，对乙肝病毒复制和HBeAg的表达也有一定的抑制作用。对细胞外和细胞内的半数有效浓度(EC_(50))分别为2.85 mM和2.75 mM，相似的选择指数约为18。二甲双胍联合应用时，可增强干扰素-α2b对乙肝病毒复制和表达的抑制作用，并对拉米夫定的表达起补充作用。二甲双胍的这种新作用部分源于它对多种乙肝病毒顺式作用元件的抑制作用。总而言之，我们的研究结果表明，二甲双胍作为一种乙肝表面抗原的生产抑制剂，可能会有潜在的临床应用价值。
Hepatitis B virus surface antigen (HBsAg) plays an important role in maintaining the tolerance and may interfere with host innate and adaptive immune responses; therefore, novel therapeutic strategies to reduce HBsAg loads in patients infected with hepatitis B virus (HBV) are emerging as an attractive but challenging issue. Metformin could regulate hepatic metabolism while the latter interacts with HBV infection. We hypothesized that metformin could affect HBsAg expression and HBV replication and may work synergistically when combined with current antivirals. In our study, a notably inhibitory effect on HBsAg production, as well as a moderate inhibition in HBV replication and HBeAg expression was observed following metformin treatment. The 50% effective concentration (EC50) for extracellular HBsAg and intracellular HBsAg in HBV‐producing HepG2.2.15 cells was 2.85 mm and 2.75 mm, respectively, with a similarly selective index of about 18. When administered in combination, metformin enhanced the inhibitory effects of interferon‐α2b on HBsAg expression and HBV replication and provided a complimentary role in HBsAg expression for lamivudine (LMV). This novel action of metformin derives partially from its inhibition on multiple HBV cis‐acting elements. By the virtues of preferably hepatocyte distribution and safety profile, collectively, our results suggest that metformin would be potentially clinically helpful as an HBsAg production inhibitor.
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影响因子：
13.5
作者：
Zhang, Xiaoyong;Zhang, Ejuan;Lu, Mengji
通讯作者：
Lu, Mengji
影响因子：
5.4
作者：
Mao, Richeng;Zhang, Jiming;Guo, Haitao
通讯作者：
Guo, Haitao
影响因子：
24.5
作者：
Chen, Hsiao-Ping;Shieh, Jeng-Jer;Wu, Chun-Ying
通讯作者：
Wu, Chun-Ying
Prospero相关同源盒蛋白（Prox1）通过抑制多个顺式调控元件抑制乙型肝炎病毒复制
影响因子：
3.8
作者：
Qin, Jun;Zhai, Jianwei;Xie, Youhua
通讯作者：
Xie, Youhua
影响因子：
5.4
作者：
Iser, David M.;Warner, Nadia;Lewin, Sharon R.
通讯作者：
Lewin, Sharon R.