(－)－Epigallocatechin-3-gallate reduces vascular endothelial growth factor expression in gastric cancer cells via suppressing activity

/Zhu Baohe

(朱寶和，Dept Gastrointestinopancreatic Surg，Affil Hosp，Sun Yat-sen Univ，Guangzhou 510080)…∥Chin J Gastrointest Surg.-2011，14(8).-631 ～635

ObjectiveTo investigate the molecular mechanism involved in the downregulation of vascular endothelial growth factor(VEGF)expression through the suppression of signal transducer and activator of transcription 3(Stat3)by(-)-Epigallocatechin-3-gallate(EGCG).MethodsAfter human gastric cancer cells(AGS)were treated with IL-6(50 μg/L)and EGCG(0，5，10，25 or 50 μmol/L)，the expression levels of VEGF，total Stat3(tStat3)，and activated Stat3(pStat3)in tumor cells were examined by Western blotting.The influence of the inhibitor of Stat3 pathway on the IL-6-induced VEGF expression was investigated.VEGF protein level in tumor cell culture medium was determined by ELISA and VEGF mRNA expression in tumor cells by RT-PCR.Tumor cell nuclear extract was prepared and nuclear expression of pStat3 was detected.Stat3-DNA binding activity was examined with chromatin immunoprecipitation(ChIP)assay.ResultsIL-6 significantly increased VEGF expression in AGS gastric cancer cells.Compared with the group without IL-6，the expression and secretion of VEGF protein，and mRNA expression increased by 2.4 fold，2.8 fold，and 3.1 fold(all P ＜0.01)，respectively.EGCG treatment markedly reduced VEGF protein，release and mRNA expression in a dose-dependent manner.When compared with the control group induced by IL-6，EGCG and AG490(a Stat3 pathway inhibitor)significantly inhibited VEGF expression induced by IL-6(P＜0.01).ECCG dose-dependently inhibited pStat3 induced by IL-6(P ＜0.05)，but not tStat3(P ＞0.05).Stat3 nuclear translocation and Stat3-DNA binding activity in AGS cells or that induced by IL-6 were directly inhibited by EGCG(P ＜0.05).ConclusionEGCG reduces expression of VEGF in gastric cancer cells through the inhibition of Stat3 activity.13refs，5 figs.