选择性COX-2抑制剂NS-398诱导白血病细胞凋亡的作用机制

目的探讨选择性环氧合酶-2(COX-2)抑制剂NS-398诱导白血病细胞系K562细胞凋亡的分子机制。方法采用流式细胞术检测细胞凋亡;采用蛋白印迹法(Western blot)检测凋亡相关蛋白Bcl-2、半胱氨酸酶-3(Caspase-3)的表达;并应用流式细胞术检测Caspase-3的活性。结果①NS-398作用K562细胞24h后,对照组未出现凋亡峰,各药物处理组(100~400μmol·L-1)均出现明显的凋亡峰,其凋亡率分别为(10.51±1.04)%、(27.79±2.40)%、(45.72±3.32)%和(60.22±2.03)%(P<0.01)。②不同浓度NS-398处理后,K562细胞中Bcl-2蛋白表达下降,而Caspase-3蛋白表达增加,与对照组相比差异具有显著性(P<0.05)。③NS-398能以剂量依赖方式促进Caspase-3活性的增加,表达活化Caspase-3的细胞百分率分别为(2.67±0.22)%、(9.53±0.15)%、(21.28±0.43)%、(39.63±0.8)%和(63.40±0.69)%(P<0.01)。结论选择性COX-2抑制剂NS-398可能通过调节Bcl-2蛋白表达、活化Caspase-3,从而诱导白血病K562细胞凋亡。

Effect of selective cyclooxygenase-2 inhibitor NS-398 on cell apoptosis in K562 cells and its underlying mechanism

Aim To investigate the effect of selective cyclooxygenase-2 inhibitor, NS-398, on cell apoptosis in leukemia cell line K562 cells and its underlying mechanism. Methods Apoptotic cell percentage was examined by flow cytometry(FCM). The protein expression of Bcl-2 and Caspase-3 was detected by Western blot, and the activity of Caspase-3 was checked by FCM. Results NS-398 induced the cell apoptosis in K562 cells in a dose-dependent manner. After NS-398 treatment, the expression of Bcl-2 protein was downregulated, whereas the expression of Caspase-3 protein was upregulated. Moreover,the activity of Caspase-3 was increased in a dose-dependent way after NS-398 treatment. Conclusion Selective cyclooxygenase-2 inhibitor,NS-398,significantly induced apoptosis in K562 cells. The underlying mechanism might be related to the downregulation of Bcl-2 and the activation of Caspase-3.