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Osimertinib联合二甲双胍对非小细胞肺癌PC 9/GR细胞的协同效应
引用本文:彭佳,袁媛,潘跃银,张颖.Osimertinib联合二甲双胍对非小细胞肺癌PC 9/GR细胞的协同效应[J].安徽医科大学学报,2017,52(7).
作者姓名:彭佳  袁媛  潘跃银  张颖
作者单位:安徽医科大学第三附属医院干部病房,合肥,230061;合肥市滨湖医院中心实验室,合肥,230061;安徽医科大学附属省立医院肿瘤科,合肥,230001
基金项目:安徽省科技攻关项目,安徽高校省级自然科学研究重点项目,安徽省卫生计生委中医药科研课题
摘    要:目的 研究Osimertinib联合二甲双胍对吉非替尼获得性耐药的非小细胞肺癌PC 9/GR细胞的生长抑制效应及其可能机制.方法 Osimertinib和二甲双胍单药或联合作用于PC 9/GR细胞后,应用MTT法检测不同药物处理组处理后对PC 9/GR细胞的抑制率影响;荧光染色法观察和流式细胞术检测Osimertinib和二甲双胍单药或联合诱导细胞凋亡的变化;Western blot法检测各药物处理组细胞磷酸化及非磷酸化的AMP依赖的蛋白激酶(AMPK)和70 ku核糖体蛋白S6激酶(P70S6K)蛋白的表达水平.结果 Osimertinib和二甲双胍双药联合作用可显著抑制PC 9/GR细胞的增殖,作用强于各单药(P<0.05),表现为协同作用(联合指数<1);双药联合时相较于单药表现出更强的诱导细胞凋亡的作用;二甲双胍可上调细胞内p-AMPK蛋白的表达,Osimertinib和二甲双胍均可下调p-P70S6K蛋白,且双药联合较单药下调p-P70S6K蛋白水平更为显著.结论 Osimertinib和二甲双胍联合用药对PC 9/GR细胞的增殖有显著抑制作用并可以促进其凋亡的发生,具有协同作用.

关 键 词:非小细胞肺癌  Osimertinib  二甲双胍  联合

Synergistic effect of Osimertinib combined with metformin on non-small cell lung cancer PC 9/GR cells
Abstract:Objective To explore the efficacy of Osimertinib combined with metformin on the growth inhibition of human non-small cell lung cancer PC 9/GR cells cells and its possible mechanism.Methods After using Osimertinib and metformin alone or in combination to treat PC 9/GR cells , the half inhibitory concentration (IC50) aswell as the combination index(CI) values were detected by the MTT method.The changes of apoptosis induced by Osimertinib and metformin alone or in combination were detected by the fluorescent microscope and flow cytometry.The change of the p-AMPK and the p-p70S6K protein level were detected by Western blot.Results The combination therapy with Osimertinib and metformin showed an synergic effect on proliferative inhibition compared to Osimertinib or metformin alone therapy(P<0.05), which showed an synergic effect(CI<1).In addition,apoptotic rates were significantly increased in combination treatment compared to the single drug.The result of the Western blot showed that metformin may upregulate the expression of p-AMPK protein;in addition, both Osimertinib and metformin could reduce the lever of p-p70S6K, the expression levels of p-p70S6K was decreased in the combination therapy compared to Osimertinib or metformin alone therapy.Conclusion The combination of Osimertinib and metformin could significantly inhibit cell proliferation and promoted cell apoptosis, and has synergistic effect.
Keywords:non-small cell lung cancer  Osimertinib  metformin  combination
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