Cyclooxygenase-2 inducingangiogenesis in pancreatic carcinoma is mediated by prostaglandin E_2
- VernacularTitle:前列腺素E_2在环氧合酶-2促胰腺癌新生血管生成中的介导作用
- Author:
Xingpeng WANG
;
Chuangao XIE
;
Yuwei DONG
- Publication Type:Journal Article
- Keywords:
Prostaglandin E_2;
Cyclooxygenase-2;
Vascular endothelial growth factor;
Pancreatic carcinoma
- From:
Chinese Journal of Digestion
2001;0(11):-
- CountryChina
- Language:Chinese
-
Abstract:
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.
