细胞周期蛋白依赖激酶Roscovitine诱导非小细胞肺癌A549细胞凋亡及其机制的研究

目的：探讨细胞周期蛋白依赖激酶（CDK）抑制剂Roseovitine（Ros）诱导非小细胞肺癌（NSCLC）A549细胞凋亡及其作用机制。方法：以不同浓度Ros（101．1M、20yM、40μM）处理细胞24h，采用AnnexinV-PI染色以流式细胞仪检测细胞凋亡，Westernblot法检测胞浆中和线粒体促凋亡蛋白Bax和Bad的表达，流式细胞仪检测线粒体膜电位（脚）变化。结果：Ros以剂量依赖的方式诱导A549细胞凋亡，同时Bad和Bax在胞浆的含量随着Ros剂量的增加而减少，而在线粒体中却出现相反的结果，线粒体膜电位随Ros剂量的增大而降低。结论：Ros可通过促进Bax和Bad由胞浆向线粒体易位，诱导NSCLCA549细胞由线粒体途径发生凋亡。

Cyclin Dependent Kinase Inhibitor Roscovitine-induced Apoptosis in Non-small Cell Lung Cancer A549 Cells and Its Mechanisms

Objective： To investigate the effect of cyclin dependent kinase inhibitor roscovitine （Ros）-induced apoptosis on non-small cell lung cancer A549 cells and its mechanisms. Methods： A549 cells were exposed to varying concentrations of Ros for 24h. Apoptosis was detected with Annexin V-PI staining by flow cytometry. The expression of pro-apoptotic protein Bax and Bad in cytoplasm and mitochondria was detected by western blot. The changes of mitochondrial membrane potential （MMP） were analyzed by flow cytometry. Results： Roscovitine could effectively induce apoptosis and this effect increased with the increasing of the drug concentration. The expression levels of Bax and Bad in the cytosol declined with Ros treatment, while increased in the mitochondria, and which was in a dose-dependent manner. Ros also caused decreasing of MMP dose-dependently. Conclusionsi Ros induced apoptosis in A549 cells in a dose-dependent way by facilitating mitochondrial translocation of Bax and Bad, thus activating mitochondrial apoptotic pathway.