Yang Xiaojun, Zhang Youcheng, Zhang Lingyi, Zhang Lin, Mao Jie
Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, China.
Cancer Lett. 2008 Nov 28;271(2):281-93. doi: 10.1016/j.canlet.2008.06.017. Epub 2008 Jul 26.
The expression of alpha-fetoprotein (AFP), a tumor-associated antigen, is silenced in normal adult hepatocyte but reactivated in human hepatocellular carcinoma (HCC). To investigate the roles of AFP in the regulation of cell growth, we silenced AFP expression in the HCC cell line Huh7 by transfection of specific Stealth RNAi. After the transfection for 48 h, the expression of AFP gene was almost abolished, the cell proliferation was inhibited by 46.15%, and the number of cells undergoing early apoptosis was significantly increased to 63.93%. Inhibition of AFP expression also resulted in an increased in Bax/Bcl-2 ratio, the release of cytochrome c from mitochondria and activation of caspase-3. The results suggest that AFP may positively regulate cell proliferation by enhancing the apoptosis resistance via dysfunction of the p53/Bax/cytochrome c/caspase-3 signaling pathway in AFP-producing HCC cell line. As such, the knockdown of AFP gene should be further investigated in vivo as a novel approach to HCC treatment.
甲胎蛋白（AFP）是一种肿瘤相关抗原，其表达在正常成年肝细胞中沉默，但在人类肝细胞癌（HCC）中重新激活。为了研究AFP在细胞生长调节中的作用，我们通过转染特异性Stealth RNAi使肝癌细胞系Huh7中的AFP表达沉默。转染48小时后，AFP基因的表达几乎被消除，细胞增殖受到46.15%的抑制，早期凋亡细胞的数量显著增加至63.93%。AFP表达的抑制还导致Bax/Bcl-2比值增加、细胞色素c从线粒体释放以及caspase-3激活。结果表明，在产生AFP的肝癌细胞系中，AFP可能通过p53/Bax/细胞色素c/caspase-3信号通路功能障碍增强抗凋亡能力来正向调节细胞增殖。因此，作为一种肝癌治疗的新方法，AFP基因敲低应在体内进一步研究。
