Molecular Carcinogenesis, 2015, 54(4):301-11.

Genistein Inhibits Hepatocellular Carcinoma Cell Migration by Reversing the Epithelial–Mesenchymal Transition: Partial Mediation by the Transcription Factor NFAT1

Weiqi Dai, Fan Wang, Lei He, et al

Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China

To investigate the effects and mechanism of genistein on hepatocellular carcinoma. Cell counting kit-8 assays showed that genistein at 3, 6, and 9 µM had no significant cytotoxic effects on HepG2, SMMC-7721, and Bel-7402 cells. Cell scratch and Transwell assays identified that genistein inhibited migration of three cell lines. In three cell lines, genistein enhanced E-cadherin and α-catenin, but reduced N-cadherin and Vimentin at both mRNA and protein levels in a dose-dependent manner. Simultaneously, treatment with genistein suppressed epithelial-mesenchymal transition (EMT) induced by TGF-β. In HepG2 cells, genistein reduced mRNA, and protein expressions of nuclear factor of activated T cells 1 (NFAT1), Abca3, Autotaxin, CD154, and Cox-2. Phorbol 12-myristate 13-acetate (PMA) and ionomycin enhanced activity of NFAT1, reduced E-cadherin and α-catenin protein levels, and increased protein levels of N-cadherin and Vimentin. Transwell demonstrated that PMA and ionomycin reversed the migration inhibitory effects of genistein on HepG2 cells. In vivo, genistein inhibited the intrahepatic metastasis by reversing the EMT, which was correlated with reduced NFAT1 . Genistein inhibited hepatocellular carcinoma cell migration by reversing the EMT, which was partly mediated by NFAT1. The fact that EMT can be reversed by genistein may shed light on the possible mechanisms for its role in liver cancer therapy.

美国《分子致癌研究》, 2015, 54(4):301-11.

金雀异黄素通过扭转上皮-间充质细胞转换抑制肝癌细胞迁移︰ 由转录因子 NFAT1 部分调节
戴伟奇，王帆，何磊，等
中国上海市同济大学医学院上海第十人民医院消化内科

探讨染料木素对肝癌细胞的作用及机制。细胞计数试剂盒-8测定显示3,6和9μM的染料木黄酮对HepG2，SMMC-7721和Bel-7402细胞没有显着的细胞毒性作用。细胞划痕和Transwell测定鉴定出染料木黄酮抑制三种细胞系的迁移。在三种细胞系中，染料木黄酮增强E-钙粘蛋白和α-连环蛋白，但以剂量依赖性方式在mRNA和蛋白质水平上降低N-钙粘蛋白和波形蛋白。同时，染料木素处理抑制TGF-β诱导的上皮 - 间质转化（EMT）。在HepG2细胞中，染料木素减少mRNA，激活的T细胞1（NFAT1），Abca3，Autotaxin，CD154和Cox-2的核因子的蛋白质表达。佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）和离子霉素增强NFAT1的活性，降低E-钙粘蛋白和α-连环蛋白水平，并增加N-钙粘蛋白和波形蛋白的蛋白质水平。 侵袭实验证明PMA和离子霉素逆转了染料木黄酮对HepG2细胞的迁移抑制作用。在体内，染料木素通过逆转EMT来抑制肝内转移，这与减少的NFAT1相关。染料木黄酮通过逆转EMT（其部分由NFAT1介导）抑制肝细胞癌细胞迁移。 EMT可以被染料木素逆转的事实可能揭示其在肝癌治疗中的作用的可能机制。