人肺腺癌耐顺铂细胞A549/CDDP获得侵袭转移能力的分子机制  

Molecular mechanism of acquisition of invasion and metastasis phenotype in human lung cancer cell line A549/CDDP

作　　者：陈新来[1] 胡惠军[1] 潘勇权 邹伟文[1] 周文泉[1] 古彩红[1] 王昊[2] 

机构地区：[1]惠州市第三人民医院病理科,广东惠州516002 [2]中山大学药学院微生物与生化药学实验室,广东广州510006

出　　处：《现代肿瘤医学》2013年第8期1670-1674,共5页Journal of Modern Oncology

基　　金：国家自然科学基金资助项目(编号:81071712)

摘　　要：目的:研究人肺腺癌耐顺铂细胞A549/CDDP获得侵袭转移能力的分子机制。方法:细胞划痕实验和Transwell侵袭实验比较A549和A549/CDDP的转移侵袭能力的差别,以及LY294002对A549/CDDP侵袭转移能力的影响。蛋白质免疫印迹技术检测AKT,NF-κB,STAT3信号通路的激活情况,MTT法检测A549和A549/CDDP对顺铂的敏感性,以及PI3K/AKT通路抑制剂LY294002对A549/CDDP细胞对顺铂的敏感性的影响。结果:A549/CDDP对顺铂的耐药性以及侵袭转移能力相对于A549有明显增强。Western blot结果表明:A549/CDDP细胞AKT通路被激活,NF-κB,STAT3通路没有明显变化。LY294002能够明显抑制A549/CDDP的侵袭转移能力并且能够提高A549/CDDP对于顺铂的敏感性。结论:A549/CDDP细胞相对于A549细胞的侵袭转移能力明显增强,其机制与PI3K/AKT信号通路的激活有关。Objective：To investigate the molecular mechanism of acquisition of invasive and migratory phenotype of cisplatin-resistant human lung cancer cell line A549/CDDP.Methods：The capability of migration and invasion of A549 cells and A549/CDDP cells and the effect of LY294002 on migration and invasion of A549/CDDP cells were detected by wound healing assay and transwell invasion assay.Western blotting was used to detect the activation of AKT,NF-κB and STAT3 signaling pathway.The sensibility of A549 cells and A549/CDDP cells to cisplatin and the effect of LY294002 on sensibility of A549/CDDP cells to cisplatin was measured by MTT assay.Results：Compared to A549 cells,the resistance of A549/CDDP cells to cisplatin and the migration and invasion were significantly enhanced.The results of western blotting demonstrated that AKT signaling pathway is activated,but not NF-κB and STAT3 signaling pathways.LY294002 suppressed migration and invasion of A549/CDDP cells and enhanced the sensibility of A549/CDDP cells to cisplatin.Conclusion：Acquisition of invasive and migratory phenotype of human lung cell line A549/CDDP is linked with activation of PI3K/AKT signaling pathway.

关 键 词：A549 CDDP 侵袭转移 耐药 PI3K AKT LY294002 

分 类 号：R730[医药卫生—肿瘤] R734.2[医药卫生—临床医学]