Nimesulide诱导胰腺癌细胞凋亡机制的研究

Pancreatic cancer cell apoptosis induced by selective cyclooxygenase2 inhibitor nimesulide mechanisms

目的:探讨选择性COX-2抑制剂Nimesulide对人胰腺癌PANC-1细胞增殖和凋亡的影响及其可能分子机制。方法:应用四甲基偶氮唑蓝(MTT)法观察不同浓度Nimesulide对PANC-1细胞增殖的影响;流式细胞术(FACS)及DNA梯状电泳(DNA ladder)检测PANC-1细胞凋亡的改变;Western blotting法检测Nimesulide不同浓度作用下PANC-1细胞COX-2蛋白水平的改变,RT-PCR法检测COX-2 mRNA水平的变化。结果:MTT、流式细胞术及DNA ladder显示Nimesulide呈剂量依赖性地抑制PANC-1细胞的增殖,并诱导其凋亡;Western blotting和RT-PCR法显示随着药物浓度的增加,COX-2蛋白及mRNA表达降低。结论:Nimesulide可能通过对COX-2表达的下调而诱导凋亡,从而抑制人胰腺癌PANC-1细胞生长。

Objective： To study the effects of selective eyclooxygenase - 2 （ COX - 2） inhibitor, nimesulide on the proliferation and apoptosis of human pancreatic carcinoma PANC - 1 cell line and its possible molecular mechanisms. Methods： The effect of nimesulide on cell proliferation was assessed by MTT assay. Apoptosis was determined by FACS analysis and DNA ladder. Western blotting and reverse transcriptase- polymerase chain reaction （RT- PCR） were used to demonstrate expression level of COX -2 protein and mRNA. Results：MTT, FACS and DNA ladder showed that nimesulide significantly decreased cell viability and induced apoptosis in pancreatic tumor PANC - 1 cell line. Western blotting and RT - PCR revealed that the protein and mRNA expression of COX - 2 were reduced by high concentration of nimesulide. Conclusion： COX - 2 selective inhibitor nimesulide inhibits proliferation, induces apoptosis of pancreatic carcinoma PANC -1 ceils via down- regulation of COX-2 expresstion.