miR-143/145基因簇调控小细胞肺癌耐药性的

冯丽萍; 苏文媚; 鲜枫; 罗亮

doi:10.3971/j.issn.1000-8578.2016.05.002

miR-143/145基因簇调控小细胞肺癌耐药性的

miR-143/145 Cluster Regulate Multi-drug Resistance of Small Cell Lung Cancer

摘要

摘要:
目的探讨miR-143/145基因簇在调控小细胞肺癌耐药性中的作用。
方法首先通过RT-PCR检测小细胞肺癌敏感细胞株（H69）和耐药细胞株（H69AR）中miR-143/145簇的差异表达；然后通过转染miR-143/145簇的模拟体（mimics）或抑制物（antagomir）增加或阻断细胞内miR-143/145的水平，通过CCK8和流式细胞技术观察细胞对化疗药物（如ADM、DDP、VP-16）敏感度的变化以及miR-143/145 mimic和antagomir对细胞周期和凋亡的影响。
结果 miR-143/145簇在H69AR细胞株中表达较H69明显增高；miR-143/145簇mimics能增加miR-143/145的表达，细胞周期发生G2/M期阻滞，细胞凋亡减少，抗凋亡蛋白BCL2的表达增加，从而引起细胞对化疗药物产生耐药；而miR-143/145簇antagomir作用与mimics相反。
结论 miR-143/145簇可能通过减少细胞的凋亡从而引起小细胞肺癌耐药。

Abstract:
Objective To explore the role of miR-143/145 cluster in regulating multi-drug resistance of small cell lung cancer(SCLC).
Methods We firstly detected the differential expression of miR-143/145 cluster in both the drug-sensitive cell line H69 and drug-resistant cell line H69AR by real-time PCR (RT-PCR). Then we transfected the cells with mimics or antagomir to increase or decrease the expression of miR-143/145 cluster. Then the sensitivities of the cells to chemotherapy drugs such as ADM, DDP, VP-16 were detected by CCK8 assay. The apoptosis rate and cell cycle were determined by flow cytometry.
Results The expression of miR-143/145 cluster was significantly higher in H69AR cells than that in H69 cells. miR-143/145 mimics could increase the expression of miR-143/145 and G2/M phase arrest, reduce cell apoptosis, and increase the expression of anti apoptotic BCL2, causing chemotherapeutic drug resistance of H69 cells; while the effect of miR-143/145 antagomir was contrary.
Conclusion miR-143/145 cluster may be associated with chemotherapy resistance of small cell lung cancer by reducing cells apoptosis.

HTML全文

参考文献(32)

施引文献

资源附件(0)