目的 研究辛伐他汀联合顺铂对人非小细胞肺癌A549细胞的抑制作用，并探讨其作用机制。方法 采用MTT法检测0.625、1.25、2.5、5、10 μmol/L顺铂和3.125、6.25、12.5、25、50 μmol/L辛伐他汀对A549细胞增殖抑制率的影响；考察2.5 μmol/L顺铂与3.125、6.25、12.5、25、50μmol/L辛伐他汀联用对A549细胞增殖抑制作用的协同效果；Annexin V-FITC/PI双染后流式细胞术检测5μmol/L顺铂与25 μmol/L辛伐他汀联合应用对对A549细胞凋亡率的影响；分光光度法检测辛伐他汀（25 μmol/L）联合顺铂（2.5 μmol/L）对A549细胞caspase-3活性的影响。结果 辛伐他汀或顺铂对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）。顺铂（2.5 μmol/L）与不同浓度（3.125、6.25、12.5、25、50 μmol/L）辛伐他汀联用对A549细胞的增殖有抑制作用，随着时间的延长，辛伐他汀剂量的增加，两者联用抑制作用呈增强的趋势（P<0.01），2.5μmol/L顺铂联用辛伐他汀25 μmol/L的抑制作用具有协同效果。25 μmol/L辛伐他汀和2.5 μmol/L顺铂能有效地诱导A549细胞的凋亡，而且两者联合使用可以显著增加A549细胞的凋亡率。25 μmol/L辛伐他汀联合2.5 μmol/L顺铂应可以显著增加A549细胞的caspase-3酶活性。结论 辛伐他汀能够显著增强顺铂对A549细胞增殖抑制、诱导凋亡的作用，可能通过上调caspase-3活性诱导A549细胞凋亡。

Objective To evaluate inhibitory effect of simvastatin combine with cisplatin onnon-small cell lung carcinoma A549 cell, and explore its mechanism. Methods Effects of 0.625, 1.25, 2.5, 5, and 10 μmol/L cisplatin and 3.125, 6.25, 12.5, 25, and 50 μmol/L simvastatin on the proliferation inhibition rate of A549 cells were determined by MTT method. Synergistic effects of 2.5 μmol/L cisplatin combined with 3.125, 6.25, 12.5, 25, and 50 μmol/L simvastatin on the proliferation inhibition of A549 cells were studied. Annexin V-FITC/PI double staining flow cytometry was used to detect the effect of 5 μmol/L cisplatin combined with 25 μmol/L simvastatin on the apoptosis rates of A549 cells. Effects of simvastatin (25 μmol/L) combined with cisplatin (2.5 μmol/L) on the caspase-3 activity of A549 cells were measured by spectrophotometry. Results Simvastatin or cisplatin 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). Cisplatin (2.5 μmol/L) combined with simvastatin with different concentrations (3.125, 6.25, 12.5, 25, and 50 μmol/L) had inhibition on proliferation of A549 cells. With time extension and simvastatin increase, the inhibition was enhanced with the trend of combination (P<0.01). Cisplatin (2.5 μmol/L) combined with simvastatin (25 μmol/L) had synergistic effect on inhibitory effects. Simvastatin (25 μmol/L) and cisplatin (2.5 μmol/L) could effectively induce apoptosis of A549 cells, and the combination could significantly increase the apoptosis rate of A549 cells. The caspase-3 activity of A549 cells could be significantly enhanced treated by simvastatin (25 μmol/L) and cisplatin (2.5 μmol/L). Conclusion Simvastatin can significantly enhance the proliferation inhibition and apoptosis induced by cisplatin in A549 cells, and it may induce apoptosis of A549 cells by up regulation of caspase-3 activity.

江西省教育厅科学技术研究项目（GJJ14688）