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-143/145mimic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。
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 H69 AR 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 H69 AR 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.
出处
《肿瘤防治研究》
CAS
CSCD
北大核心
2016年第5期326-330,共5页
Cancer Research on Prevention and Treatment
