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- 2018
NOX4抑制剂GKT137831增强顺铂对A549细胞的毒性作用
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Abstract:
摘要 目的： 研究GKT137831(NOX4抑制剂)和顺铂单用或联用对肺癌A549细胞增殖和凋亡的影响及作用机制. 方法MTT法检测不同浓度的GKT137831和顺铂对细胞毒性的影响,分别选取合适的浓度进行联合用药;流式细胞法检测细胞凋亡率;酶联免疫法检测Caspase3/7活性;免疫印迹检测 A549 细胞中 Akt、p-Akt、MRP1蛋白表达. 结果GKT137831和顺铂单用均能抑制A549细胞的增殖,并诱导其凋亡,GKT137831可增强顺铂的细胞毒性.顺铂能上调p-Akt和MRP1的表达(P<0.05),GKT137831则抑制p-Akt和MRP1的表达(P<0.05);与对照组和单独用药组相比,联合用药能抑制p-Akt和MRP1的表达(P<0.05),表明GKT137831能抑制顺铂导致的p-Akt和MRP1表达上调. 结论GKT137831能够增强顺铂对肺癌细胞A549的毒性效应,作用机制可能通过抑制PI3K/AKT途径,调节其下游 MRP1的表达有关.
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