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

Cyclooxygenase-2 inducingangiogenesis in pancreatic carcinoma is mediated by prostaglandin E_2

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PC 3细胞血管内皮生长因子 (VEGF)和PGE2 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PC 3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PGE2 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 ,PC 3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Cele brex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。

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.