Epigallocatechin-3-gallate inhibits angiogenesis of gastric cancer induced by IL-6 and its mechanism

Objective To investigate the inhibitory effect of(-)-Epigallocatechin-3-gallate(EGCG) on angiogenesis of gastric cancer induced by IL-6 and its molecular mechanism.Methods AGS gastric cancer cells were cultured with IL-6(50 ng/mL) or with a series of concentrations of EGCC.Protein levels of vascular endothelial growth factor(VEGF) in tumor cells were examined by Western blot,the VEGF release in tumor culture medium was determined by ELISA,and VEGF mRNA expression in tumor cells by RT-PCR.The conditioned media from gastric cancer cells were prepared for culturing human umbilical vein endothelial cells(HUVEC).Vascular endothelial cell proliferation was measured with MTT assay,in vitro angiogenesis was determined with endothelial cell tube formation assay in Matrigel,and angiogenesis in vivo was measured with Matrigel plug assay.Results The VEGF protein level,release and mRNA expression were increased in the IL-6 induced AGS cells by 2.4,2.8 and 3.1 folds,respectively.EGCG treatment significantly inhibited the IL-6 induced increase in level and release of VEGF protein and in mRNA expression in a dose-dependent manner.The proliferation and tube formation of vascular endothelial cells induced by IL-6 in vitro were markedly inhibited by VEGF neutralizing antibody and EGCG.The angiogenesis in vivo induced by IL-6 was also markedly inhibited by VEGF neutralizing antibody and EGCG.Conclusions EGCG reduces expression of VEGF induced by IL-6 in gastric cancer cells,and thereby inhibits tumor angiogenesis.