EGCG对胃癌血管新生中VEGF信号通路的多靶点作用

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

目的:探讨EGCG对胃癌血管生成抑制作用及其信号通路。方法:建立裸鼠异位胃癌模型,经腹腔注射EGCG,检测肿瘤生长及肿瘤组织微血管密度;不同浓度EGCG处理胃癌细胞24 h,检测胃癌VEGF蛋白和mRNA表达及VEGF分泌;同时不同浓度EGCG处理脐静脉内皮细胞,检测内皮细胞生长、迁移和体外小管形成。结果:EGCG显著抑制胃癌生长和肿瘤血管生成,平均肿瘤抑制率60.4%;EGCG显著抑制胃癌VEGF蛋白、mRNA表达和VEGF分泌;EGCG时间和剂量依赖性地抑制VEGF诱导的内皮细胞增殖,同时也剂量依赖性地抑制VEGF诱导的内皮细胞的迁移和小管生成。结论:EGCG多靶点作用于VEGF信号通路,抑制胃癌生长和血管生成。

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.