Nutrition & Cancer, 2013, 65(7):1034-41.

Genistein Induces G2/M Arrest in Gastric Cancer Cells by Increasing the Tumor Suppressor PTEN Expression

Yan-Long Liu, Guo-Qiang Zhang, Yue Yang, et al

Department of Colorectal Surgery , the Third Affiliated Hospital of Harbin Medical University , Harbin , China

Genistein, a major isoflavone found in soybeans, exhibits anticarcinogenic properties. The inhibitory effect of genistein on cell proliferation is associated with G2/M cell cycle arrest and inhibition of cdc2 activities. Here we assessed the role of PTEN in regulation of genistein-mediated G2/M cell cycle arrest in the gastric cancer cell lines (SGC-7901 and BGC-823). After 24 h following treatment, genistein induced a concentration-dependent accumulation of cells in the G2/M phase of the cell cycle. The sustained G2/M arrest by genistein in SGC-7901 and BGC-823 cells is associated with increased phospho-cdc2 (Tyr15) and decreased cdc2 protein. Genistein treatment increased Wee1 levels and decreased phospho-Wee1 (Ser 642). Moreover, genistein substantially decreased the Ser473 and Thr308 phosphorylation of Akt and upregulated PTEN expression. Downregulation of PTEN by siRNA in genistein-treated cells increased phospho-Wee1 (Ser642), whereas decreased phospho-Cdc2 (Tyr15), resulting in decreased the G2/M cell cycle arrest. Therefore, induction of G2/M cell cycle arrest by genistein involved upregulation of PTEN.

美国《营养与癌症》，2013年9月

在胃癌细胞中金雀异黄素诱导 G2/M 期中止通过提高肿瘤抑制因子PTEN的表达

刘延龙、 张国强、 杨越，等

中国哈尔滨医科大学第三附属医院结直肠手术科

金雀异黄素，一种在大豆中发现的主要异黄酮，具有抗癌性能。金雀异黄素对细胞增殖的抑制作用与 G2/M 期细胞周期阻滞和cdc2 活性抑制相关。在这里，我们评估了抑癌基因 PTEN 在调控金雀异黄素介导 的胃癌细胞（SGC-7901 和 BGC- 823）G2/M 期细胞周期阻滞中的作用。在治疗的 24 小时后, 金雀异黄素诱导细胞周期处于G2/M 期的细胞进行浓度依赖性积累。金雀异黄素使SGC-7901 和BGC-823 细胞保持连续的 G2/M 期阻滞与提高磷-cdc2 (Tyr15)和减少 cdc2 蛋白相关。金雀异黄素治疗 法提高了Wee1 的水平，降低了磷-Wee1 (Ser 642)。此外，金雀异黄素大幅减少了Ak t的Ser473 和 Thr308 磷酸化并上调 PTEN的 蛋白表达。在金雀异黄素治疗的细胞中抑癌基因 PTEN由siRNA下调提高了磷-Wee1 (Ser642) ，而降低了磷-Cdc2 (Tyr15)，从而导致G2/M 期细胞周期阻滞减少。因此，金雀异黄素诱导G2/M 期细胞周期的阻滞包括抑癌基因 PTEN 的上调。