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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: To observe the effect of cyclooxygenase-2 (COX-2) inhibitor Celecoxib on the proliferation and apoptosis of hepatocellular carcinoma cells and to explore the clinical significance of its application in the treatment of hepatocellular carcinoma. Methods: The effect of Celecoxib on the proliferation of hepatoma cells was observed by MTT method. The effect of Cele-coxib on the apoptosis of hepatocellular carcinoma cells was observed by transmission electron microscopy and flow cytometry. The cell cycle and the expression of P-gp were detected by RT-PCR Technical observation COX-2, Survivin mRNA expression changes after drug treatment. Results: Celecoxib inhibited cell proliferation and induced apoptosis in a time-and dose-dependent manner. The cell cycle distribution was changed and the proportion of cells in G_0 / G_1 phase was increased. The expression of Survivin gene was significantly down-regulated during the apoptosis of hepatoma cells with high expression of Survivin , MDR / P-gp expression weakened. CONCLUSION: Celecoxib may play an antitumor effect by inducing cell apoptosis, decreasing the expression of COX-2, affecting the cell cycle distribution, and may be equally effective in MDR cells by down-regulating the expression of Survivin and COX-2, which has important clinical significance.