Celecoxib抗肝癌作用及临床意义

Study on Effects and Significances of Celecoxib on Hepatocarcinoma

目的：观察特异性环氧合酶-2(cyclooxygenase-2,COX-2)抑制剂Celecoxib对肝癌细胞增殖和凋亡的影响,探讨应用于肝癌治疗的临床意义。方法：用MTT法观察Celecoxib对肝癌细胞增殖的影响；透射电镜及流式细胞仪观察Cele- coxib诱导肝癌细胞凋亡的作用、对细胞周期的影响及P-gp表达的变化；用RT-PCR技术观察COX-2、Survivin mRNA药物处理后表达的变化。结果：Celecoxib对肝癌细胞抑制增殖、诱导凋亡呈时间和剂量依赖性；细胞周期分布改变,G_0/G_1期细胞比例增加；在Survivin高表达的肝癌细胞凋亡过程中,Survivin基因的表达显著下调,MDR/P-gp表达减弱。结论：Celecoxib可能通过诱导细胞凋亡、降低COX-2表达、影响细胞周期分布,发挥抗肿瘤作用；并且可能通过下调Survivin、COX-2表达而对MDR细胞同样有效,有重要的临床应用意义。

Objective：The present study was designed to investigate the effects of Celecoxib, a selective COX-2 inhibitor ,on hepatocarcinoma cells and its significances used on hepatocarcinoma. Methods： Effects of celecoxib on growths of hepatocarcinoma cells were evaluated by MTT; Apoptosis of hepatoearcinoma cells （Bel07402, highly expressed COX-2 and HepG2, lower expressed COX-2 ）induced by celecoxib and P-gp expressions were detected by electron microscopy and flow cytometry. Ex- pression of COX-2 and Survivin were analyzed by reverse transcription polymerase chain reaction （RT-PCR）. Results：Inhibitory effects of celecoxib on hepatocarcinoma cells were time-and concentration-dependent ;Substantial apoptosis induced by celecoxib could be revealed under electron microscopy and by flow cytometry. The percentages of Go/ G1 phase cells increased and S phase cells fell compared with the controls（ P〈0. 01 ） and other groups. Survivin was down-regulated significantly by celecoxib . Expressions of P-gp reduced as times gone after treating by celecoxib. Conclusion; Findings of this study suggested that celecoxib acts effectively on the growth and apoptosis of hepatocarcinoma cells no matter whether MDR is highly or lowly expressed, so it＇s probably used on hepatocarcinoma therapy.