PROTEOMICS, 2012, 12(14):2391-9.

Genistein-induced mitotic arrest of gastric cancer cells by downregulating KIF20A, a proteomics study

Guang Rong Yan, Fei Yan Zou, Bian Li Dang, et al

Institute of Life and Health Engineering, and National Engineering and Research Center for Genetic Medicine, Jinan University, Guangzhou, China

Genistein exerts its anticarcinogenic effects by inducing G2/M arrest and apoptosis of cancer cells. However, the precise molecular mechanism of action of genistein has not been completely elucidated. In this study, we used quantitative proteomics to identify the genistein-induced protein alterations in gastric cancer cells and investigate the molecular mechanism responsible for the anti-cancer actions of genistein. Total 86 proteins were identified to be regulated by genistein, most of which were clustered into the regulation of cell division and G2/M transition, consistent with the anti-cancer effect of genistein. Many proteins including kinesin family proteins, TPX2, CDCA8, and CIT were identified for the first time to be regulated by genistein. Interestingly, five kinesin family proteins including KIF11, KIF20A, KIF22, KIF23, and CENPF were found to be simultaneously downregulated by genistein. Significantly decreased KIF20A was selected for further functional studies. The silencing of KIF20A inhibited cell viability and induced G2/M arrest, similar to the effects of genistein treatment in gastric cancer. And the silencing of KIF20A also increased cancer cell sensitivity to genistein inhibition, whereas overexpression of KIF20A markedly attenuated genistein-induced cell viability inhibition and G2/M arrest. These observations suggested that KIF20A played an important role in anti-cancer actions of genistein, and thus may be a potential molecular target for drug intervention of gastric cancer.

德国《蛋白质组学》，2012年8月

金雀异黄素通过下调KIF20A诱导胃癌细胞有丝分裂中止，一项蛋白质组学研究

严广荣，周飞燕，党卞力，等

中国广州暨南大学国家工程技术遗传医学研究中心生命和健康工程研究所

金雀异黄素通过诱导 G2/M 期阻滞和癌症细胞凋亡发挥其抗癌的作用。然而，金雀异黄素精确的分子机制尚未完全阐明。在此研究中，我们使用定量蛋白质组学来确认在胃癌细胞中金雀异黄素诱导的蛋白质变化并探究金雀异黄素的抗癌作用的分子机制。总共有 86种 蛋白质被确定由金雀异黄素调控，其中的大部分集中用于调节细胞分裂和 G2/M 期过渡，与金雀异黄素的抗肿瘤效果一致。包括动力蛋白家族、TPX2、 CDCA8和CIT等在内的很多蛋白质第一次被确认会受金雀异黄素的调控。有趣的是，包括 KIF11、 KIF20A、 KIF22、 KIF23 和 CENPF在内的的五种动力蛋白被发现同时被金雀异黄素下调。选择显著降低的 KIF20A 进行进一步功能性研究。沉默的 KIF20A 抑制细胞活性并诱导 G2/M 期阻滞，类似于金雀异黄素在胃癌组织中的治疗效果。沉默的 KIF20A 也增加了癌症细胞对金雀异黄素抑制的敏感性，而过表达的KIF20A则明显减弱了金雀异黄素诱导的细胞活性抑制和 G2/M 期阻滞。这些结果表明 KIF20A 在金雀异黄素进行的抗癌行动中扮演了重要的角色，因此可能成为潜在的药物干预胃癌的分子靶向。