Resveratrol Helps Recovery from Fatty Liver and Protects against Hepatocellular Carcinoma Induced by Hepatitis B Virus X Protein in a Mouse Model
Resveratrol Helps Recovery from Fatty Liver and Protects against Hepatocellular Carcinoma Induced by Hepatitis B Virus X Protein in a Mouse Model
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DOI：
10.1158/1940-6207.capr-12-0001
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发表时间：
2012-07-01
影响因子：
3.3
通讯作者：
Tsai, Ting-Fen
中科院分区：
文献类型：
--
作者：
Lin, Hsiu-Ching;Chen, Yi-Fan;Tsai, Ting-Fen
白藜芦醇是一种天然多酚，对各种物种和各种疾病模型都有有益的影响。在这里，我们使用HBVX蛋白(HBX)转基因小鼠来研究白藜芦醇是否对乙肝病毒(HBVX)相关的肝细胞癌(HCC)有效。我们发现白藜芦醇(30 mg/kg/d)对HBx诱导的脂肪肝和早期肝损伤有治疗作用。白藜芦醇可减少细胞内的活性氧，并短暂刺激肝细胞的增殖。有趣的是，白藜芦醇抑制了LXRα，并下调了脂肪生成基因Srebp1-c和PPAR Gamma的表达。Srebp1-c基因的减少似乎进一步下调了其靶基因ACC和Fas的表达。此外，白藜芦醇还能刺激AMPK和SirT1的活性。因此，白藜芦醇对HBx转基因小鼠具有抑制脂肪生成、促进短暂肝再生和刺激抗氧化活性的多效性作用。此外，在较晚的癌前阶段，白藜芦醇延缓了HBX介导的肝癌的发生，并将肝癌发病率从80%降低到15%，减少了5.3倍。白藜芦醇可作为一种潜在的乙肝相关肝癌的化学预防药物。癌症前传；5(7)；952-62。(C)2012年AACR。
Resveratrol is a natural polyphenol that has beneficial effects across species and various disease models. Here, we investigate whether resveratrol is effective against hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) usingHBVX protein (HBx) transgenic mice. We found that resveratrol (30 mg/kg/d) has a therapeutic effect on HBx-induced fatty liver and the early stages of liver damage. Resveratrol decreased intracellular reactive oxygen species and transiently stimulated hepatocyte proliferation. Interestingly, resveratrol inhibited LXR alpha and downregulated the expression of the lipogenic genes, Srebp1-c and PPAR gamma. The decrease in Srebp1-c seems to further downregulate the expression of its target genes, Acc and Fas. In addition, resveratrol stimulated the activity of Ampk and SirT1. Thus, resveratrol has a pleiotropic effect on HBx transgenic mice in terms of the downregulation of lipogenesis, the promotion of transient liver regeneration, and the stimulation of antioxidant activity. Furthermore, at the later precancerous stages, resveratrol delayed HBx-mediated hepatocarcinogenesis and reduced HCC incidence from 80% to 15%, a 5.3-fold reduction. Resveratrol should be considered as a potential chemopreventive agent for HBV-associated HCC. Cancer Prev Res; 5(7); 952-62. (C) 2012 AACR.