以Celecoxib为基础的联合方案对宫颈癌细胞抑制作用的研究

目的:探讨环氧化酶-2(cox-2)抑制剂Celecoxib与化疗药顺铂(DDP)联合应用对人宫颈癌Hela细胞的作用及机制。方法:用免疫细胞化学SP法检测Hela细胞cox-2蛋白表达后,将Celecoxib、DDP单独或联合处理Hela细胞,用MTT法检测细胞增殖的抑制率,流式细胞仪检测细胞周期及凋亡。结果:Celecoxib可下调Hela细胞cox-2蛋白表达,抑制其增殖作用呈浓度和时间依赖性。在一定浓度范围内DDP也抑制Hela细胞生长,作用呈量效关系。Celecoxib与DDP联合应用后抗增殖作用较单一用药显著增强(P<0.05),DDP浓度≥1 mg/L时两者有协同或相加作用。Celecoxib及DDP均可有效诱导Hela细胞凋亡,联用凋亡率明显增加并出现G0-G1期细胞阻滞。结论:Celecoxib与DDP联用可通过抑制增殖、诱导细胞凋亡和细胞周期阻滞对Hela细胞有协同抗肿瘤效应,提示两者联合可能在宫颈癌临床治疗上具有潜在价值。

Study of Inhibiting Effects of Celecoxib-based Combination on Human Cervical Cancer Hela Cell Line

Objective: To investigate the effects of cyclooxygenase-2(cox-2) selective inhibitor,Celecoxib,combined with Cisplatin(DDP) on human cervical cancer Hela cell line and the possible mechanism.Methods: Cox-2 protein expression was detected by immunocytochemistry using isozyme selective antibodies.After treatment of Hela cells with Celecoxib,DDP or combination of both,the inhibitory rate of cells was measured by methabenzthiazuron(MTT) assay,cell cycle and apoptosis were analyzed by flow cytometry.Results: Celecoxib down-regulated the cox-2 protein expression of Hela cells and inhibited the cell proliferation in a concentration-dependent and time-dependent manner.DDP could inhibit the growth of cells in a dose-dependent manner too.When Celecoxib and DDP(≥1 mg/L) were combined,the inhibitory effect was remarkable enhanced in a synergistic or additive pattern(P<0.05).Celecoxib(120 μmol/L) and DDP(2.5 mg/L) could respectively induce the apoptosis of Hela cells and cause G_(0)-G_(1) cell cycle arrest,and this effect of apoptosis induction was increased when combinated Celecoxib with DDP.Conclusion: Celecoxib combined with DDP shows synergistic anti-tumor effects by enhancement of growth inhibition and apoptosis induction in Hela cell line,which indicate this combination may have a potential value in cervical cancer therapy.