前列腺素E2在环氧合酶-2促胰腺癌新生血管生成中的介导作用

目的 探讨环氧合酶-2(COX-2)促进胰腺癌新生血管生成过程中前列腺素E2(PGE2)的介导作用，进一步揭示COX-2促进胰腺癌生长的机制。方法 体外培养胰腺癌细胞株PC-3，分别应用酶联免疫吸附(ELISA)和放射免疫(RIA)等方法，检测选择性COX-2抑制剂Celebrex对胰腺癌PC3细胞血管内皮生长因子(VEGF)和PGR表达的调节作用，并观察外源性PGE2对Celebrex调节VEGF表达的干预。建立裸鼠PC3细胞移植瘤，Western印迹检测Celebrex对胰腺癌组织VEGF表达的影响，RIA测定Celebrex对胰腺癌组织PGB变化的调节。结果 随着Celebrex作用浓度的提高以及作用时间的延长，PC3细胞分泌的VEGF和PGE2受到抑制，呈时间和剂量依赖性。外源性PGE2显著上调Celebrex作用后PC-3细胞VEGF蛋白表达，呈剂量依赖性，体内实验表明，Celebrex可显著抑制移植瘤组织VEGF和PGE2的表达。结论 COX-2参与了PC-3细胞VEGF分泌的调节，进而促进胰腺癌新生血管形成，而PGE2则在该过程中起着重要的介导作用。

Cyclooxygenase-2 inducing angiogenesis in pancreatic carcinoma is mediated by prostaglandin E2

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.