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《Chinese Journal of Digestion》 2003-11
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Cyclooxygenase-2 inducingangiogenesis in pancreatic carcinoma is mediated by prostaglandin E_2

WANG Xing-peng, XIE Chuan-gao,DONG Yu-wei, et al. Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai 200080, China  
Objective To investigate the effects of cyclooxygenase-2 (COX-2) on the expressions of vascular endothelial growth factor (VEGF) and prostaglandin E_2 (PGE_2) in pancreatic carcinoma both in vitro and in vivo, and to clarify the possible mechanism of PGE_2 in mediating COX-2 inducing angiogenesis of pancreatic carcinoma. Methods In vitro study, the inhibitory effects of Celebrex, a selective cyclooxygenase-2 inhibitor, on the expression of VEGF and PGE_2 in pancreatic carcinoma cell lines PC-3 were determined using either enzyme-linked immuno-absorbent assay (ELISA) or radioimmunoassay (RIA). Effect of exogenous PGE_2 on the down-regulation of VEGF by Celebrex was also assessed. In vivo study, PC-3 cell line xenograft nude mice model was established. Changes of VEGF expression and PGE_2 of tumor tissues after the treatment of Celebrex were investigated using Western blotting or RIA. Results Celebrex suppressed the expressions of VEGF and PGE_2 in cultured PC-3 cell line with a manner of dose- and time-dependence. Exogenous PGE_2 up-regulated the expression of VEGF, which was suppressed by Celebrex in a dose-dependent fashion. In vivo study, administration of Celebrex into xenograft nude mice inhibited expressions of VEGF and PGE_2 significantly. Conclusion COX-2 is involved in angiogenesis in pancreatic carcinoma probably through the inhibition of the production of angiogenic factors such as VEGF. PGE_2 is likely to act as an important mediator in this process.
【Fund】: 上海市科技发展基金重点项目 (9941190 16)
【CateGory Index】: R735.9
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