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作 者:赵洁婷 钟文[2] 徐建平 ZHAO Jieting ZH XU Jianping(Department of Pathology , Anhui Chest Ho sp i ta l , Hefei , Anhui 230022 , China Department of Pathology, Anhui Provincial Hospital ,Hefei , Anhui 230001 , China)
机构地区:[1]安徽省胸科医院病理科,安徽合肥230022 [2]安徽省立医院病理科,安徽合肥230001
出 处:《安徽医药》2017年第6期1082-1086,共5页Anhui Medical and Pharmaceutical Journal
基 金:安徽省自然科学基金项目(1608085QH217)
摘 要:目的研究microRNA-21(miR-21)对人肺腺癌细胞A549对于顺铂耐药性的影响及分子机制。方法 MTT法检测A549和顺铂耐药株A549/CDDP对于顺铂的敏感性,以及在A549细胞中过表达miR-21和在A549/CDDP细胞中抑制miR-21表达后对顺铂敏感性的影响;RT-PCR方法检测A549和A549/CDDP中miR-21表达情况;Western blotting检测PI3K/AKT,核因子-κB(NF-κB)信号通路的激活情况以及在过表达miR-21和抑制miR-21表达后细胞中AKT信号通路的活性变化情况。结果相对于A549细胞,A549/CDDP对顺铂的敏感性有明显降低,而细胞中miR-21表达则明显增多。Western blotting结果表明:与A549细胞相比,A549/CDDP细胞PI3K/AKT通路被激活,NF-κB通路没有明显变化。过表达miR-21可以激活PI3K/AKT信号通路并提高A549细胞对顺铂的耐药性,相反地,抑制miR-21表达抑制了A549/CDDP细胞中的AKT通路的活化情况并降低了A549/CDDP细胞对顺铂的耐药性。结论 miR-21可以促进肺癌细胞A549对顺铂的耐药性,其机制与PI3K/AKT信号通路的激活有关。Objective To investigate the molecular mechanism of microRNA-21 (miR-21) induced-drug resistance in human lung cell line A549 cells.Methods The sensibility of A549 cells and A549/CDDP cells to cisplatin and the effect of miR-21 on sensibility of A549 cells or A549/CDDP cells to cisplatin was measured by MTT assay.The expression of miR-21 in A549 cells and A549/CDDP cells was detected by RT-PCR.Western blotting was used to detect the activation of AKT and NF-κB signaling pathways.Results Compared to A549 cells,the resistance of A549/CDDP cells to cisplatin was significantly enhanced and the expression of miR-21 in A549/CDDP cells was also increased.The results of western blotting demonstrated that AKT signaling pathway,not NF-κB signaling pathway was activated.MiR-21 overexpression decreased the sensibility of A549 cells to cisplatin and activated AKT signaling pathway.Conversely,inhibition of miR-21 expression increased the sensibility of A549/CDDP cell to cisplatin and suppressed the activity of AKT signaling pathway.Conclusions miR-21 can induce drug resistance of human lung cell line A549 to cisplatin and molecular mechanism involve in activation of PI3K/AKT signaling pathway.
关 键 词:肺癌 MICRORNA-21 耐药 PI3K/AKT
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