(-)-Epigallocatechin-3-gallate inhibits growth of gastric cancer by reducing VEGF production and angiogenesis.

AIM

To investigate the effect of (-)-epigallocatechin-3-gallate (EGCG) on growth of gastric cancer and its possible mechanism.

METHODS

Heterotopic tumors were induced by subcutaneously injection of SGC-7901 cells in nude mice. Tumor growth was measured by calipers in two dimensions. Tumor angiogenesis was determined with tumor microvessel density (MVD) by immunohistology. Vascular endothelial growth factor (VEGF) protein level and activation of signal transducer and activator of transcription 3 (Stat3) were examined by Western blotting. VEGF mRNA expression was determined by RT-PCR and VEGF release in tumor culture medium by ELISA. VEGF-induced cell proliferation was studied by MTT assay, cell migration by gelatin modified Boyden chamber (Transwell) and in vitro angiogenesis by endothelial tube formation in Matrigel.

RESULTS

Intraperitoneal injection of EGCG inhibited the growth of gastric cancer by 60.4%. MVD in tumor tissues treated with EGCG was markedly reduced. EGCG treatment 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. This inhibitory effect was associated with reduced activation of Stat3, but EGCG treatment did not change the total Stat3 expression. EGCG also inhibited VEGF-induced endothelial cell proliferation, migration and tube formation.

CONCLUSION

EGCG inhibits the growth of gastric cancer by reducing VEGF production and angiogenesis, and is a promising candidate for anti-angiogenic treatment of gastric cancer.