miR-126增加非小细胞肺癌细胞A549对顺铂的敏感性

miR-126在多种恶性肿瘤中存在表达下调并显示抑癌基因的功能，然而其在肿瘤敏感性中的作用仍不明确.为了探讨miR-126在非小细胞肺癌细胞A549对顺式铂氨(cis-diammine dichloroplatoum, cisplatin, CDDP)敏感性中的作用及可能机制，本研究用MTS法检测非小细胞肺癌细胞A549及其衍生的CDDP耐受细胞A549/DDP对CDDP的敏感性.结果表明，A549/DDP细胞对CDDP的耐受性是A549细胞的4.05倍(P=0.0078)|用qRT-PCR检测发现,相比于A549细胞，A549/DDP细胞中miR-126的表达下调了8.45倍(P=0.0063)，而survivin和Bcl-2的表达明显上调|通过MTS、qRT-PCR及Western印迹实验发现,miR-126 mimics使A549/DDP细胞中miR-126的表达上调了12.63倍(P=0.0013)，并明显增加A549/DDP细胞对CDDP的敏感性及下调survivin和Bcl-2的表达;相反，miR-126 inhibitor能明显增加A549细胞对CDDP的耐受性及增加survivin和Bcl-2的表达.本研究结果提示,miR-126在非小细胞肺癌CDDP耐受细胞中的表达下调,上调miR-126的表达能增加耐药细胞对CDDP的敏感性. miR-126是逆转肺癌CDDP耐受的可能潜在靶标.

miR-126 Sensitizes the Human Non-small Cell Lung Cancer A549 Cells to Cisplatin

miR-126 is downregulated in several cancer types and shows tumor suppressive role, but its role in therapeutic response remains unclear. This study is to explore the role and possible mechanism of miR-126 in the chromosensitivity of human non small cell lung cancer A549 cells to cis-diamminedichloroplatoum (cisplatin, CDDP). In the present study, MTS assay was used to detect the cytotoxic activity of CDDP on A549 and A549/DDP cells and showed the resistance index (RI) of A549/DDP cells to CDDP was 4.83 (P=0.0078). Results from qRT-PCR and Western blot showed the expression of miR-126 decreased 8.45 fold (P=0.0063）in A549/DDP cells and the expression of survivin and Bcl-2 increased at both mRNA and protein level. Ectopic expression of miR-126 with mimics significantly downregulated survivin and Bcl-2 expression in A549/DDP cells and sensitized A549/DDP cells to CDDP. Conversely, miR-126 inhibitor upregulated survivin and Bcl-2 expression in A549 cells and enhanced the resistance of A549 cells to CDDP. Thus, miR-126 expression decreases in CDDP resistant A549/DDP cells and restored miR-126 expression increases the chemosensitivity of the A549/DDP cells to CDDP, suggesting miR-126 is a potential target to prevent CDDP resistance in human non small cell lung cancer．