Gao Feng, Deng Gang, Liu Wenbin, Zhou Kechao, Li Ming
Department of Ultrasonography, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
Department of Hepatobiliary and Pancreatic Surgery, The Third Xiangya Hospital of Central South University, Changsha, P.R. China.
Oncol Rep. 2017 Feb;37(2):1203-1211. doi: 10.3892/or.2017.5347. Epub 2017 Jan 3.
Resveratrol, one of the major polyphenols found in red wine, is suggested to have a role as a chemo-prevention or chemotherapy agent in various human cancer models. Herein, we report that resveratrol has a profound antitumor effect on human hepatocellular carcinoma (HCC) cells by down-regulation of the HGF-c-Met signaling pathway. Resveratrol inhibited anchorage-dependent and -independent growth of HCC cells in a dose-dependent manner. Short-term resveratrol exposure substantially decreased HGF-induced c-Met signaling pathway activation, and long-term exposure to resveratrol markedly inhibited c-Met expression on the cell membrane. Additionally, resveratrol suppressed HGF-induced cell invasion, and knockdown of c-Met decreased the sensitivity of HCC cells to resveratrol treatment. Finally, the antitumor activity of resveratrol was validated in xenograft model and resveratrol prominently restrained tumor growth in vivo. In summary, our results suggested that c-Met offers a candidate molecular target for hepatocellular carcinoma management.
白藜芦醇是红酒中发现的主要多酚类物质之一，在各种人类癌症模型中，它被认为具有化学预防或化疗药物的作用。在此，我们报告白藜芦醇通过下调HGF-c-Met信号通路对人肝癌（HCC）细胞具有显著的抗肿瘤作用。白藜芦醇以剂量依赖的方式抑制HCC细胞的贴壁依赖性和非贴壁依赖性生长。短期暴露于白藜芦醇可显著降低HGF诱导的c-Met信号通路激活，长期暴露于白藜芦醇可显著抑制细胞膜上c-Met的表达。此外，白藜芦醇抑制HGF诱导的细胞侵袭，敲低c-Met可降低HCC细胞对白藜芦醇治疗的敏感性。最后，在异种移植模型中验证了白藜芦醇的抗肿瘤活性，白藜芦醇在体内显著抑制肿瘤生长。总之，我们的结果表明c-Met为肝癌治疗提供了一个候选分子靶点。
