COX-2抑制剂Nimesulide抗肺癌作用及其机制研究  

Study of Influence and Mechanism of Cyclooxygenase-2 Inhibitor Nimesulide Anti-lung Cancer Cells

作　　者：张卿[1] 

机构地区：[1]内蒙古医学院附属医院呼吸内科,内蒙古呼和浩特010050

出　　处：《内蒙古医学杂志》2009年第11期1281-1284,F0004,共5页Inner Mongolia Medical Journal

基　　金：国家自然科学基金资助项目(课题号30560175)

摘　　要：目的:流行病学资料显示,非甾体类抗炎药物阿司匹林能降低肺癌的发病率。我们的目的是探讨Nimesulide-一种选择性COX-2抑制剂对肺癌A549细胞增殖的影响及其机制。方法:采用MTT比色法观察Nimesulide对A549细胞生长的影响,采用放射免疫法(ELISA)测定Nimesulide对肺癌A549细胞上清液中前列腺E2(PGE2)释放的影响,免疫细胞化学法测定肺癌A549细胞中COX-2、PCNA、bcl-2基因蛋白表达水平。结果:Nimesulide呈时间、剂量依赖性抑制A549细胞增殖,抑制率最低22.73%,最高72.04%;以剂量依赖性方式抑制A549细胞PGE2释放;Nimesulide可抑制A549细胞PCNA、bcl-2的蛋白表达,而对COX-2蛋白表达无影响。结论:Nimesulide以时间、剂量依赖性方式抑制肺癌A549细胞增殖,其机制可能与抑制肺癌A549细胞PGE2释放,并下调A549细胞PCNA、bcl-2的蛋白表达有关,而对COX-2的蛋白表达无影响。选择性COX-2抑制剂Nimesulide有可能在肺癌防治中发挥重要作用。Objective：Recently Epidemiology data indicate a reduction in the incidence of lung cancer using nonstaredal anti-inflammation drugs （NSAIDs）-Aspirin.The aim of our study was to explicit Nimesulide,a selective COX-2 inhibitor,on proliferation of A549 cells and its mechanism.Methods： MTT assay were used to determine the influence of Nimesulide on proliferation A549 cells.Radioimmunoassay was used to detect the influence of nimesulide on PGE2 content in culture supernatant of A549 cells.Immunocytochemistry （sp） method were used to assess protein expression COX-2、PCNA、bcl-2 genes in A549 cells treated by nimesulide in order to explicate the influence and mechanism of nimesulid on proliferation of A549 cells.Results：Nimesulide inhibited the A549 cells proliferation in a time-and dose-dependent manner.The lowest inhibition rate produced by Nimesulide in A549 cells was 22.73% and the most highest inhibition rate was 72.04%.PGE2 were decreased sharply in culture supernatant after 24 h nimesulide-treated cells and PGE2 production was reduced with the nimesulide dose increasing（P〈0.01）.Nimesulide had the effect of downregulation protein expression of PCNA、bcl-2 in human lung cancer A549 cells and did not inhibit the COX-2 protein expression of A549 cell s（P〈0.01）.Conclusion： Nimesulide has growth-and proliferation-inhibitory effects on lung cancer A549 cells in a time-and dose-dependent manner.It is considered that the mechanism may be involved in nimesulide by inhibiting PGE2 production of A549 cells and COX-2 activity without affecting the COX-2 protein expression and by down regulating protein expression of PCNA、bcl-2,which may be likely contributed to an important mechanism in anti neoplastic of nimesulide on A549 cells.It suggests that Nimesulide is very important significance in prevention and treatment of lung cancer and may be a new chemitherapy agent of NSCLC.

关 键 词：NIMESULIDE 肺癌 增殖 蛋白 表达 

分 类 号：R734.2[医药卫生—肿瘤]