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白藜芦醇通过PTEN调控的PI3K/Akt信号通路诱导人胃癌MGC803细胞的细胞周期阻滞。

Resveratrol induces cell cycle arrest in human gastric cancer MGC803 cells via the PTEN-regulated PI3K/Akt signaling pathway.

作者信息

Jing Xiaoping, Cheng Weiwei, Wang Shiying, Li Pin, He Li

机构信息

Department of Traditional Chinese Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040, P.R. China.

Department of General Surgery, Putuo Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China.

出版信息

Oncol Rep. 2016 Jan;35(1):472-8. doi: 10.3892/or.2015.4384. Epub 2015 Nov 3.

Abstract

Resveratrol is a polyphenolic compound that is extracted from Polygonum cuspidatum and is used in traditional Chinese medicine. Previous data have shown that resveratrol inhibits the growth of human gastric cancer. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] and trypan blue assays showed that resveratrol significantly decreased the survival rate of MGC803 cells in a concentration- and time-dependent manner. Our flow cytometric analysis showed that resveratrol treatment arrested the cells at the G0/G1 phase of the cell cycle. Furthermore, western blotting demonstrated that resveratrol decreased the protein expression of phospho-glycogen synthase kinase 3β (p-GSK3β), cyclin D1, phospho-phosphatase and tensin homologue (p-PTEN), phospho-phosphatidylinositol 3'-OH kinase (p-PI3K), and phospho-protein kinase B (p-PKB/Akt). We also found that resveratrol inhibited the progression of the cell cycle in MGC803 cells by repressing p-PI3K and p-Akt expression. Meanwhile, resveratrol did not decrease the phosphorylation level of Akt when the PTEN gene expression was knocked down by an siRNA in the MGC803 cells. Taken together, these results suggest that resveratrol induced cell cycle arrest in human gastric cancer MGC803 cells by regulating the PTEN/PI3K/Akt signaling pathway.

摘要

白藜芦醇是一种从虎杖中提取的多酚类化合物,用于传统中药。先前的数据表明,白藜芦醇可抑制人胃癌的生长。MTT [3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐] 和台盼蓝试验表明,白藜芦醇以浓度和时间依赖性方式显著降低MGC803细胞的存活率。我们的流式细胞术分析表明,白藜芦醇处理使细胞停滞在细胞周期的G0/G1期。此外,蛋白质印迹法表明,白藜芦醇降低了磷酸化糖原合酶激酶3β (p-GSK3β)、细胞周期蛋白D1、磷酸化磷酸酶和张力蛋白同源物 (p-PTEN)、磷酸化磷脂酰肌醇3'-OH激酶 (p-PI3K) 和磷酸化蛋白激酶B (p-PKB/Akt) 的蛋白表达。我们还发现,白藜芦醇通过抑制p-PI3K和p-Akt的表达来抑制MGC803细胞的细胞周期进程。同时,当PTEN基因表达在MGC803细胞中被小干扰RNA敲低时,白藜芦醇并没有降低Akt的磷酸化水平。综上所述,这些结果表明白藜芦醇通过调节PTEN/PI3K/Akt信号通路诱导人胃癌MGC803细胞的细胞周期停滞。

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