氯喹与拓扑替康联用协同抑制A549肺癌细胞株的增殖

目的观察氯喹(CQ)与拓扑替康(TPT)联用对A549肺癌细胞株的影响,为增敏化疗及氯喹在抗肿瘤方面的研究、开发和临床应用提供理论支持和实验依据。方法 MTT法检测细胞抑制率,取对数生长期的肺癌细胞A549种于96孔板内6,×103个/孔2,00μL/孔。实验分为对照组(注射用水)和实验组,实验组加入0.05～25.6μg/mL的TPT,分别培养48 h和72 h;实验组加入不同浓度的单药或以固定比例(TPT∶CQ=1∶10)联合药物,TPT/CQ为0.39/3.90、.78/7.8、1.56/15.6、3.13/31.3和6.25/62.5μg/mL;37℃放置4 h后,弃上清液,加入100μLDMSO,摇床上摇匀使紫色结晶充分溶解。用酶标仪测定波长为570 nm处的吸光度(OD)值,计算细胞生长抑制率。细胞生长抑制率=(1-实验组平均OD值/对照组平均OD值)×100%。每组实验重复3次。结果应用浓度为0～25μg/mL TPT处理A549细胞48 h和72 h,通过MTT检测可发现TPT对A549细胞的生长抑制呈现时间及浓度依赖性,在72 hI,C50值为(1.769±0.288)μg/mL,CQ(0.39～6.25μg/mL)与TPT(3.9～62.5μg/mL)联用对A549细胞的增殖抑制作用,通过软件分析在上述浓度范围内,两药的联合指数(CI)均<1。结论 CQ能增强TPT对A549细胞的增殖抑制作用。

The combination of CQ and TPT produced synergic effect on inhibiting the proliferation of A549 cells

Objective To investigates the effects of topotecan(TPT) and chloroquine(CQ) combined treatment on the proliferation of A549 human lung cancer cell line.Methods A549 cells in logarithmic growth phase were divided into control groups and experimental groups,in which they were exposed to 0.05~25.6 μg/mL TPT and the combination of TPT and CQ(the ratio of TPT to CQ was 1/10),respectively,for both 48 and 72 hours.The TPT/CQ concentration gradients were 0.39/3.9,0.78/7.8,1.56/15.6,3.13/31.3 and 6.25/62.5 μg/mL.Cell proliferation and combination index(CI) were evaluated by MTT cell viability assay.Results Exposure to TPT resulted in significantly dose-and time-dependent inhibition of cell viability in A549 cells.At 72 hour,the IC50 was(1.769±0.288)μg/mL.Synergic inhibition of cell proliferation in A549 cells was revealed in combination of CQ(0.39~6.25 μg/mL) and TPT(3.9~62.5 μg/mL) for 72 hours,with CI less than 1.Conclusion CQ sensitized A549 cells to TPT treatment in vitro.