二甲双胍对肺腺癌耐厄洛替尼细胞株A549ER的耐药逆转作用

目的 探讨二甲双胍对人肺腺癌耐厄洛替尼细胞株A549ER的耐药逆转作用.方法 将人肺腺癌细胞株A549细胞设为亲本组;将耐厄洛替尼细胞株A549ER细胞分为空白对照组、厄洛替尼组、二甲双胍组和联合用药组（厄洛替尼±二甲双胍组）,采用CCK8法检测不同浓度药物作用下各组细胞的50％抑制浓度（IC50）,计算耐药倍数和逆转倍数.采用流式细胞术检测各组A549ER细胞的凋亡率和细胞周期,计算增殖指数.结果 在0 ～ 20 mmol/L浓度范围内,二甲双胍对A549细胞及A549ER细胞均有生长抑制作用,抑制率随二甲双胍浓度升高而增加.厄洛替尼对A549细胞和A549ER的IC50分别为15.15 μmol/L和118.8 μmol/L,A549ER的耐药倍数为7.84.联合用药组A549ER细胞IC50为73.55 umol/L,耐药倍数为4.85.二甲双胍对A549ER厄洛替尼耐药性的逆转倍数为1.62.空白对照组、厄洛替尼组、二甲双胍组和联合用药组的凋亡率分别为（5.53±3.00）％、（7.51±3.73）％、（10.25 ±4.23）％和（16.92±1.20）％.根据细胞周期结果计算空白对照组、厄洛替尼组、二甲双胍组和联合用药组的增殖指数分别为0.84±0.15、0.78 ±0.10、0.73±0.08和0.60 ±0.09.结论 A549ER细胞较A549细胞对厄洛替尼有明显的耐药性;二甲双胍对A549ER细胞厄洛替尼的耐药性具有逆转作用;二甲双胍通过抑制细胞生长、促进细胞凋亡、减缓细胞周期进程等途径逆转A549ER细胞耐药.

Metformin reverses the resistance of erlotinib-resistant human lung adenocarcinoma cell line A549ER in vitro

Objective To detect the resistance reversal effects of metformin on erlotinib-resistant human lung adenocarcinoma cell line A549ER.Methods The human lung adenocarcinoma cell line A549 was defined as parental group.The erlotinib-resistant human lung adenocarcinoma cell line A549ER was set as blank group.A549ER treated with erlotinib alone was erlotinib group.A549ER treated metformin alone was metformin group.A549ER treated with erlotinib and metformin was combination group.The growth inhibitory effects of erlotinib on parental group A549 cell,erlotinib group A549ER cell and combination group A549ER cell were detected with CCK8 assay,and the half maximal inhibitory concentration （IC50）,resistance index and reversal index were calculated.The cell cycle and cell apoptosis of blank group,erlotinib group,metformin group and combination group A549ER cell were detected with flow cytometry,and the proliferation index were calculated.Results The metformin inhibit growth of A549 and A549ER and the inhibition increased with increasing concentration.The IC50 of erlotinib on parental group A549 cell,erlotinib group A549ER cell and combination group A549ER cell were 15.15μmol/L,118.8 μmol/L and 73.55μmol/L,respectively.The resistance index of erlotinib group A549ER cell and combination group A549ER cell were 7.84 and 4.85,respectively.The reversal index of metformin on the resistance of erlotinib was 1.62.The cell apoptosis rates of blank group A549ER cell,erlotinib group A549ER cell,metformin group A549ER cell and combination group A549ER cell were （5.53 ±3.00）％,（7.51 ±3.73）％,（10.25 ±4.23）％ and （16.92± 1.20）％,respectively.The cell apoptosis rate of combination group A549ER cell was significant higher compared with the other there groups （P ＜0.05）.The proliferation index of blank group A549ER cell,erlotinib group A549ER cell,metformin group A549ER cell and combination group A549ER cell were 0.84 ±0.15,0.78 ±0.10,0.73 ± ± 0.08 and 0.60 ± 0.09,respectively.Conclusions A549ER has signi