目的 研究辛伐他汀聯(lián)合順鉑對(duì)人非小細(xì)胞肺癌A549細(xì)胞的抑制作用，并探討其作用機(jī)制。方法 采用MTT法檢測(cè)0.625、1.25、2.5、5、10 μmol/L順鉑和3.125、6.25、12.5、25、50 μmol/L辛伐他汀對(duì)A549細(xì)胞增殖抑制率的影響；考察2.5 μmol/L順鉑與3.125、6.25、12.5、25、50μmol/L辛伐他汀聯(lián)用對(duì)A549細(xì)胞增殖抑制作用的協(xié)同效果；Annexin V-FITC/PI雙染后流式細(xì)胞術(shù)檢測(cè)5μmol/L順鉑與25 μmol/L辛伐他汀聯(lián)合應(yīng)用對(duì)對(duì)A549細(xì)胞凋亡率的影響；分光光度法檢測(cè)辛伐他?。?5 μmol/L）聯(lián)合順鉑（2.5 μmol/L）對(duì)A549細(xì)胞caspase-3活性的影響。結(jié)果 辛伐他汀或順鉑對(duì)A549細(xì)胞的增殖有顯著的抑制作用，隨著濃度的增加、時(shí)間的延長，呈時(shí)間、劑量相關(guān)性，其抑制作用增強(qiáng)（P<0.01）。順鉑（2.5 μmol/L）與不同濃度（3.125、6.25、12.5、25、50 μmol/L）辛伐他汀聯(lián)用對(duì)A549細(xì)胞的增殖有抑制作用，隨著時(shí)間的延長，辛伐他汀劑量的增加，兩者聯(lián)用抑制作用呈增強(qiáng)的趨勢(shì)（P<0.01），2.5μmol/L順鉑聯(lián)用辛伐他汀25 μmol/L的抑制作用具有協(xié)同效果。25 μmol/L辛伐他汀和2.5 μmol/L順鉑能有效地誘導(dǎo)A549細(xì)胞的凋亡，而且兩者聯(lián)合使用可以顯著增加A549細(xì)胞的凋亡率。25 μmol/L辛伐他汀聯(lián)合2.5 μmol/L順鉑應(yīng)可以顯著增加A549細(xì)胞的caspase-3酶活性。結(jié)論 辛伐他汀能夠顯著增強(qiáng)順鉑對(duì)A549細(xì)胞增殖抑制、誘導(dǎo)凋亡的作用，可能通過上調(diào)caspase-3活性誘導(dǎo)A549細(xì)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.

江西省教育廳科學(xué)技術(shù)研究項(xiàng)目（GJJ14688）