[關鍵詞]
[摘要]
目的 研究辛伐他汀聯(lián)合順鉑對人非小細胞肺癌A549細胞的抑制作用,并探討其作用機制。方法 采用MTT法檢測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A549細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A549細胞增殖抑制作用的協(xié)同效果;Annexin V-FITC/PI雙染后流式細胞術檢測5μmol/L順鉑與25 μmol/L辛伐他汀聯(lián)合應用對對A549細胞凋亡率的影響;分光光度法檢測辛伐他汀(25 μmol/L)聯(lián)合順鉑(2.5 μmol/L)對A549細胞caspase-3活性的影響。結果 辛伐他汀或順鉑對A549細胞的增殖有顯著的抑制作用,隨著濃度的增加、時間的延長,呈時間、劑量相關性,其抑制作用增強(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A549細胞的增殖有抑制作用,隨著時間的延長,辛伐他汀劑量的增加,兩者聯(lián)用抑制作用呈增強的趨勢(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A549細胞的凋亡,而且兩者聯(lián)合使用可以顯著增加A549細胞的凋亡率。25 μmol/L辛伐他汀聯(lián)合2.5 μmol/L順鉑應可以顯著增加A549細胞的caspase-3酶活性。結論 辛伐他汀能夠顯著增強順鉑對A549細胞增殖抑制、誘導凋亡的作用,可能通過上調(diào)caspase-3活性誘導A549細胞凋亡。
[Key word]
[Abstract]
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.
[中圖分類號]
[基金項目]
江西省教育廳科學技術研究項目(GJJ14688)