JOURNAL ARTICLE

[Epigallocatechin-3-gallate inhibits growth and angiogenesis of gastric cancer and its molecular mechanism]

Bao-He Zhu, Wen-Hua Zhan, Yu-Long He, Shi-Rong Cai, Zhao Wang, Chang-Hua Zhang
Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery 2009, 12 (1): 82-5
19145512

OBJECTIVE: To investigate the inhibitory effect of epigallocatechin-3-gallate (EGCG) on growth and angiogenesis of gastric cancer and to explore its molecular mechanism.

METHODS: Heterotopic tumor was established by subcutaneously injection with SGC-7901 cells in nude mice. Once the tumor was established, the mice were allocated randomly into two groups and received intraperitoneal injection of EGCG or phosphate buffered saline respectively. Tumor growth was measured by caliper in two dimensions, and angiogenesis was determined with tumor microvessel density (MVD) by immunohistochemistry. Protein levels of vascular endothelial growth factor (VEGF) and activation of signal transducer and activator of transcription 3(Stat3) in tumor cells and tumor tissues were examined by Western blot. VEGF release in tumor culture medium was determined by ELISA and VEGF mRNA expression in tumor cells by RT-PCR.

RESULTS: Intraperitoneal injection of EGCG significantly inhibited the growth of gastric cancer[(0.32+/-0.08) g vs(0.81+/-0.12) g, t=7.24, P<0.01], and an average of 60.4% suppression of primary tumor growth was observed. Microvessel density in tumor tissues receiving EGCG treatment was also markedly reduced(15.2+/-4.3 vs 24.6+/-6.6,t=3.41,P<0.01),and an average of 38.2% suppression was observed. 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. This inhibitory effect was associated with reduced activation of Stat3. Stat3 activation was dose-dependently suppressed by EGCG in tumor cells, and an average of 53.5% reduction was observed in tumor tissues, but EGCG treatment did not change total Stat3 expression.

CONCLUSION: EGCG reduces expression of VEGF in gastric cancer by inhibiting activation of Stat3, thereby inhibits tumor growth and angiogenesis of gastric cancer.

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