Epigallocatechin-3-gallate inhibits angiogenesis of gastric cancer by targeting VEGF signaling pathway

Objective:To investigate the inhibitory effect of(-)-Epigallocatechin-3-gallate(EGCG) on angiogenesis of gastric cancer and its signaling pathway.Methods: Heterotopic tumors were established by subcutaneously injection of SGC-7901 cells in the dorsal area of nude mice.When tumors reached a volume of 50 mm3,the mice were randomized into two groups and received intraperitoneal injection of EGCG or phosphate buffered saline(PBS),respectively.Tumor growth was measured by caliper in two dimensions,and tumor angiogenesis was determined with tumor microvessel density(MVD) by immunohistology.SGC-7901 cells were treated with EGCG at different concentrations for 24 h,vascular endothelial growth factor(VEGF) protein level in tumor cells and tissues were examined by Western blot,VEGF release in tumor cell culture media by ELISA and VEGF mRNA expression in tumor cells by RT-PCR.VEGF-induced cell proliferation of human umbilical vein endothelial cells(HUVECs) was studied by MTT assay,cell migration by gelatin modified Boyden chamber(Transwell) and in vitro angiogenesis by endothelial cell tube formation in Matrigel.Results: The mean weight of tumors treated with EGCG was significantly lower than that of control group,and an average of 60.4% suppression of primary tumor growth was observed.The tumor growth curve in test group was markedly lower than that in control group.Microvessel density in tumor tissues receiving EGCG treatment was also markedly reduced.EGCG treatment markedly reduced VEGF protein level in vitro and in vivo.Secretion and mRNA expression of VEGF in tumor cells were also suppressed by EGCG in a dose-dependent manner.EGCG also inhibited VEGF-induced endothelial cells proliferation,migration and tube formation.Conclusion:EGCG inhibits growth and angiogenesis of gastric cancer by multiply targeting VEGF signaling pathway.