托瑞米芬逆转肺癌耐药细胞株A549/cDDP耐药性的研究

Reversal effect of toremifene(TOR) on A549/cDDP lung cancer cell line with resistance to cisplatin

目的:探讨托瑞米芬(TOR)对耐顺铂(cDDP)细胞株A549的逆转作用,为临床应用提供实验数据。方法:用不同浓度的托瑞米芬单独及与cDDP联合与耐药细胞A549共同培养,通过MTT法和流式细胞仪法检测其对A549/cDDP的逆转及增敏效果。结果:经不同浓度的托瑞米芬单独及与cDDP联合与耐药细胞A549共同培养后,单独TOR(5μmol/L、10μmol/L)对A549/cDDP细胞的增殖均无明显影响,各组间数据无明显差异(P>0.05)。当cDDP与TOR联合作用时无论TOR终浓度5μmol/L或10μmol/L,均能明显增加cDDP对A549/cDDP细胞的敏感性(P<0.05,P<0.001)。其IC50值分别为39.06μmol/L和30.64μmol/L,逆转倍数分别为2.05倍和2.65倍。cDDP+TOR终浓度5μmol/L与cDDP+TOR终浓度10μmol/L之间除了在cDDP浓度为200μmol/L时两者有差异(P<0.05)外其它均无明显差异。结论:托瑞米芬与DDP联合应用可以提高A549/cDDP的逆转及治疗效果。

Objective：To investigate the reversal effect of toremifene（TOR） on A549/cDDP lung cancer cell line,which resistance to cisplatin,and provide the experimental data for clinical application.Methods：A549 cell line was cultured with different concentrations of toremifene,with or without cisplatin.Sensitive effect of toremifene on A549/cDDP was measured by MTT assay.The cell apoptotic activity was determined with Annexin V/PI staining by flow cytometry.Results：Using TOR（5 μmol / L,10 μmol / L） alone had no significant effect on proliferation of A549/cDDP cell line（P0.05）,but TOR combined with cDDP（the final concentration of TOR was 5 μmol/L or 10 μmol/L） significantly increased the sensitive effect of A549/cDDP cells to cDDP（P0.05,P0.001）.The value of IC50 elevated up to 39.06 μmol/L and 30.64 μmol/L,and the fold of reversal effect was 2.05 and 2.65 times,respectively.In addition to 200 μmol/L of cDDP,there was no significant differences between 5 μmol/L and 10 μmol/L of cDDP combined with TOR.Conclusion：Toremifene combined with cDDP could reverse the resistance to cDDP,and improve the treatment effect on A549/cDDP cells.