(-)-Epigallocatechin-3-gallate inhibits VEGF expression induced by IL-6 via Stat3 in gastric cancer

查看全文 作　　者：Bao-He [1,2]Zhu;Hua-Yun [1]Chen;Wen-Hua [1]Zhan;Cheng-You [2]Wang;Shi-Rong [1]Cai;Zhao [1]Wang;Chang-Hua [1]Zhang;Yu-Long [1]He

机构地区：[1]Department ofGastrointestinal and Pancreatic Surgery, First Affiliated Hospital,Sun Yat-Sen University, Gastric Cancer Center of Sun Yat-SenUniversity, Guangzhou 510080, Guangdong Province, China;[2]Department of General Surgery, First Affiliated Hospital, Shenzhen University, Shenzhen518035, Guangdong Province, China

出　　处：《World Journal of Gastroenterology》索引2011年第17卷第18期,共11页

基　　金：Supported by National Natural Science Foundation of China, Grant, No. 30571833;Natural Science Foundation of Guangdong Province, 05001785;China Postdoctoral Science Foundation 20100470963 摘　　要：AIM: To demonstrate that (-)-Epigallocatechin-3-gallate (EGCG) inhibits vascular endothelial growth factor (VEGF) expression and angiogenesis induced by interleukin-6 (IL-6) via suppressing signal transducer and activator of transcription 3 (Stat3) activity in gastric cancer. METHODS: Human gastric cancer (AGS) cells were treated with IL-6 (50 ng/mL) and EGCG at different concentrations. VEGF, total Stat3 and activated Stat3 protein levels in the cell lyses were examined by Western blotting, VEGF protein level in the conditionedmedium was measured by enzyme-linked immunosorbent assay, and the level of VEGF mRNA was evaluated by reverse transcription polymerase chain reaction (RTPCR). Stat3 nuclear translocation was determined by Western blotting with nuclear extract, and Stat3-DNA binding activity was examined with Chromatin immunoprecipitation (ChIP) assay. IL-6 induced endothelial cell proliferation was measured with 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazoliumbromide assay, in vitro angiogenesis was determined with endothelial cell tube formation assay in Matrigel, and IL-6-induced angiogenesis in vitro was measured with Matrigel plug assay. RESULTS: There was a basal expression and secretion of VEGF in AGS cells. After stimulation with IL-6, VEGF expression was apparently up-regulated and a 2.4-fold increase was observed. VEGF secretion in the conditioned medium was also increased by 2.8 folds. When treated with EGCG, VEGF expression and secretion were dose-dependently decreased. IL-6 also increased VEGF mRNA expression by 3.1 folds. EGCG treatment suppressed VEGF mRNA expression in a dose-dependent manner. EGCG dose-dependently inhibited Stat3 activation induced by IL-6, but did not change the total Stat3 expression. When treated with EGCG or AG490, VEGF expressions were reduced to the level or an even lower level in the tumor cells not stimulated with IL-6. However, PD98059 and LY294002 did not change VEGF expression induced by IL-6. EGCG inhibited Stat3 nucleus translocation, and Stat3-DNA binding activity was also markedly decreased by EGCG. Furthermore, EGCG inhibited IL-6 induced vascular endothelial cell proliferation and tube formation in vitro and angiogenesis in vitro . CONCLUSION: EGCG inhibits IL-6-induced VEGF expression and angiogenesis via suppressing Stat3 activity in gastric cancer, which has provided a novel mechanistic insight into the anti-angiogenic activity of EGCG. 关键词：表没食子儿茶素没食子酸酯血管内皮生长因子 STAT3 体外诱导胃癌细胞 DNA结合活性逆转录聚合酶链反应内皮细胞增殖

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(-)-Epigallocatechin-3-gallate inhibits VEGF expression induced by IL-6 via Stat3 in gastric cancer

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