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


CONCLUSIONS
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.
Zhu
Bao-He
BH
Department of Gastrointestinal and Pancreatic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Gastric Center of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China.
Zhan
Wen-Hua
WH
Li
Zheng-Rong
ZR
Wang
Zhao
Z
He
Yu-Long
YL
Peng
Jun-Sheng
JS
Cai
Shi-Rong
SR
Ma
Jin-Ping
JP
Zhang
Chang-Hua
CH
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D050796:STAT3 Transcription Factor / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
D016588:Anticarcinogenic Agents; D050796:STAT3 Transcription Factor; D042461:Vascular Endothelial Growth Factor A; D002392:Catechin; C045651:epigallocatechin gallate