辛伐他汀对人肺腺癌细胞的凋亡作用及其调控机制研究

Effect of Simvastatin on Apoptosis of Human Lung Adenocarcinoma Cells and Its Regulatory Mechanism

目的:研究辛伐他汀对人非小细胞肺癌A549细胞的抑制作用,并探讨其作用机制。方法:MTT法检测0、12.5、25、50μmol·L^(-1)辛伐他汀对A549细胞增殖抑制率的影响;Annexin V-FITC/PI双染后流式细胞术检测不同浓度辛伐他汀(0、12.5、25、50μmol·L^(-1))对A549细胞凋亡率的影响;分光光度法检测不同浓度辛伐他汀(0、12.5、25、50μmol·L^(-1))对A549细胞caspase-3活性的影响。结果:辛伐他汀对A549细胞的增殖有显著的抑制作用,随着浓度的增加、时间的延长,呈时间、剂量相关性,其抑制作用增强(P<0.01)。辛伐他汀能有效地诱导A549细胞的凋亡,随着浓度的增加,凋亡率增加。辛伐他汀显著增加A549细胞的caspase-3酶的活性,且呈剂量相关性。结论:辛伐他汀对人肺癌A549细胞有增殖抑制作用,并且具有显著的浓度及时间依赖性,辛伐他汀通过增加细胞Caspase-3的活性诱导A549细胞凋亡。

Objective： To evaluate the inhibitory effect of simvastatin on non-small cell lung carcinoma A549 cells and to explore its mechanism.Methods： Effects of 0,12.5,25,and 50 μmol·L-1 simvastatin on the proliferation inhibition rate of A549 cells were determined by MTT method.Annexin V-FITC/PI double staining flow cytometry was used to detect the effect of 0,12.5,25 and 50 μmol·L-1 simvastatin for 48 h on the apoptosis rates of A549 cells.The effects of simvastatin（0,12.5,25 and 50 μmol·L-1） on the caspase-3 activity of A549 cells were measured by spectrophotometry.Results： Simvastatin could significantly inhibit the proliferation of A549 cells in a concentration-and time-dependent manner.With the increase of concentration and the prolongation of time,the inhibitory effect was enhanced（P 〈 0.01）.Simvastatin effectively induced the apoptosis of A549 cells in a concentration-dependent manner.With the increase of concentration,the inhibitory effect was enhanced（P 〈 0.01）.Caspase-3 activity of A549 cells could be significantly enhanced after treated by simvastatin in a concentration-dependent manner.Conclusion： Simvastatin can significantly inhibit the proliferation of A549 cells with a remarkable concentration-and time-dependence,and it may induce the apoptosis of A549 cells by increasing the activity of caspase-3.