上调miRNA-506对肺癌耐药细胞株A549/DDP耐药性的逆转及其机制

目的:探讨微小核糖核酸（miRNA）-506对人非小细胞肺癌顺铂耐药株A549/DDP细胞耐药性的逆转及其可能机制。方法:构建miRNA-506 模拟物，应用脂质体法转染A549/DDP细胞。应用实时逆转录酶链聚合反应（qRT-PCR）法验证各组细胞中miRNA-506的表达情况，CCK8法检测顺铂对细胞的抑制作用。流式细胞术Annexin V／PI双染检测各组细胞的凋亡。Western blot检测MDR1、MRP1、Bcl-2、Bax的蛋白表达。结果:qRT-PCR结果显示，miRNA-506转染组miRNA-506的表达量明显高于对照组（P<0.05）。CCK8结果显示，上调miRNA-506 增强A549/DDP细胞对顺铂的敏感性。流式细胞术结果显示上调miRNA-506 促进顺铂诱导的A549/DDP细胞凋亡。上调miRNA-506可以使A549/DDP细胞MDR1、MRP1和Bcl-2蛋白的表达下降，使Bax蛋白的表达升高。结论:上调miRNA-506能逆转A549/DDP细胞对顺铂的耐药，这一过程可能通过miRNA-506调控多药耐药蛋白和凋亡相关蛋白实现。

The reversing and molecular mechanisms of miR-503 on the drug-resistance to cisplatin in A549/DDP cells

Objective:The aim of this study is to investigate the effects and molecular mechanisms of miRNA-506 on enhancing the sensitivity of cisplatin-resistance in lung cancer cell line A549/DDP.Methods:Synthetic miRNA-506 and its negative control were transfected into A549/DDP cells by liposome method.After transfection，the expression of miRNA-506 level was detected by quantitative real-time PCR.CCK8 assay was performed to determine the effect of miRNA-506 on A549/DDP sensitivity to cisplatin.Cell apoptosis rate were determined by flow cytometry，the expression of multi-drugs resistant proteins MDR1，MRP1，Bcl-2 and Bax were determined by Western blot.Results:The results of qRT-PCR show that the miRNA-506 expression in transfection group was up-regulated than control group.miRNA-506 was able to increase the cisplatin sensitivity of A549/DDP.Flow cytometry showed that upregulation of miRNA-506 promoted cisplatin-induced apoptosis in A549/DDP cells.Upregulation of miRNA-506 can decrease the expression of MDR1，MRP1 and Bcl-2 protein and increase the expression of Bax protein in A549/DDP cells.Conclusion:miRNA-56 was able to reverse the cisplatin resistance of A549/DDP by inhibiting the drug efflux and promoting cell apoptosis.