Anti-HBV drugs suppress the growth of HBV-related hepatoma cells via down-regulation of hepatitis B virus X protein. (28th April 2017)

• Record Type: Journal Article
• Authors: Zhang, Shuqin; Gao, Shan; Zhao, Man; Liu, Yunxia; Bu, Yanan; Jiang, Qiulei; Zhao, Qiang; Ye, Lihong; Zhang, Xiaodong
• Is Part Of: Cancer letters. Volume 392(2017)
• Page Start: 94
• Page End: 104
• Publication Date: 2017-04-28
• Subjects: LdT -- ETV -- IFN-α2b -- HCC -- HBx; HCC hepatocellular carcinoma -- HBV hepatitis B virus -- HBx hepatitis B virus X protein -- HBV-Tg mice HBV-transgenic mice -- NAs nucleos(t)ide analogues -- LdT telbivudine -- ETV entecavir -- IFN-α2b interferon-α2b -- NF-κB nuclear factor-κB -- AP-1 activator protein 1 -- PCNA proliferating cell nuclear antigen -- ERK extracellular signal-related kinases -- YAP Yes-associated protein -- ROS reactive oxygen species -- MTT 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide -- E2F1 E2-promoter binding factor 1 -- IHC immunohistochemical staining; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2017.02.003
• Languages: English
• ISSNs: 0304-3835

Abstract

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. Highlights: Anti-HBV drugs (LdT, ETV and IFN-α2b) are able to suppress the growth of HBV-expressing hepatoma cells in vitro and in vivo . LdT, ETV and IFN-α2b can inhibit the proliferation of HBV-related hepatoma cells through inhibiting HBV production. HBx contributes to the inhibition of proliferation of HBV-related hepatoma cells mediated by LdT, ETV and IFN-α2b. Combination application of anti-HBV drugs is better than single use in anti-proliferation of HBV-related hepatoma cells.