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


CONCLUSIONS
EGCG reduces expression of VEGF in gastric cancer by inhibiting activation of Stat3, thereby inhibits tumor growth and angiogenesis of gastric cancer.
Zhu
Bao-He
BH
Department of Gastrointestinopancreatic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Zhan
Wen-Hua
WH
He
Yu-Long
YL
Cai
Shi-Rong
SR
Wang
Zhao
Z
Zhang
Chang-Hua
CH
D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D002392:Catechin; C045651:epigallocatechin gallate