title: [(-)-Epigallocatechin-3-gallate reduces vascular endothelial growth factor expression in gastric cancer cells via suppressing activity].
abstract: OBJECTIVE
  To 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).
  
  
  METHODS
  After 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.
  
  
  RESULTS
  IL-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). EGCG 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).
  
  
  CONCLUSIONS
  EGCG reduces expression of VEGF in gastric cancer cells through the inhibition of Stat3 activity.
authors.affiliation: Department of Gastrointestinopancreatic Surgery, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Bao-he
authors.initials: BH
authors.lastname: Zhu
authors.forename: Yu-long
authors.initials: YL
authors.lastname: He
authors.forename: Wen-hua
authors.initials: WH
authors.lastname: Zhan
authors.forename: Shi-rong
authors.initials: SR
authors.lastname: Cai
authors.forename: Zhao
authors.initials: Z
authors.lastname: Wang
authors.forename: Chang-hua
authors.initials: CH
authors.lastname: Zhang
authors.forename: Hua-yun
authors.initials: HY
authors.lastname: Chen
mesh_terms: D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D002392:Catechin; C045651:epigallocatechin gallate