miR-181d对小细胞肺癌化疗药物敏感性的影响  

Effect of miR-181d on chemo-sensitivity in human small cell lung cancer

作　　者：王云涛[1] 白义凤[2] 胡洪林[2] 许峰[1] 

机构地区：[1]四川大学华西医学院肿瘤中心,成都市610041 [2]四川省人民医院

出　　处：《中国肿瘤临床》2015年第6期345-350,共6页Chinese Journal of Clinical Oncology

摘　　要：目的:探讨miR-181d在调节小细胞肺癌化疗敏感性中的作用。方法:通过QRT-PCR和Western blot检测小细胞肺癌敏感细胞株H69及耐药细胞株H69AR中miR-181d的差异表达。上调H69AR细胞中的miR-181d表达,检测miR-181d和BCL2表达;通过CCK8检测细胞对各种化疗药物(ADM、DDP、VP-16)的敏感性变化,QRT-PCR检测87例小细胞肺癌组织标本中miR-181d表达,所有患者均接受EP方案(依托泊苷+顺铂)化疗,分析其与患者预后及生存时间的关系。结果:miR-181d在H69AR及对化疗耐药患者中呈低表达,同时伴随着BCL2高表达(P<0.001)。上调miR-181d能降低BCL2表达水平,增加H69AR细胞对化疗药物(ADM、DDP、VP-16)的敏感性(P<0.01)。miR-181d的表达与肿瘤的分期、对化疗药物的敏感性及生存时间相关(P<0.001),高表达miR-181d的患者总生存时间(OS)和无进展生存时间(DFS)较低表达者延长(P<0.001)。结论:miR-181d可能在小细胞肺癌多药耐药中发挥着重要的作用,miR-181d可望作为评价小细胞肺癌疗效的预测指标。Objective：To investigate the possible role of miR-181d in regulating the multidrug resistance （MDR） of small cell lung cancer （SCLC） and its clinical significance. Methods： Quantitative reverse transcriptase-polymerase chain reaction （QRT-PCR） and Western blot were used to investigate the differential expression of miR-181d and BCL2 from mRNA and protein levels in the chemo-sensitivity cell H69 and the chemo-resistance cell H69AR. The miR-181d expression in H69AR was then upregulated. More-over, CCK8 assay was employed to detect the sensitivities of the cells to chemotherapy drugs, such as ADM, DDP, and VP-16. Mean-while, the expression of miR-181d in the specimens of 87 cases with SCLC were detected using QRT-PCR. All patients received the chemotherapeutic regimen of EP （etoposide＋cisplatin）. Correlation of the miR-181d expression with clinicopathological features, prog-nosis, and survival time of the patients was studied. Results：miR-181d was downregulated in the SCLC multidrug-resistant cell line H69AR and chemo-resistant patients. Moreover, miR-181d was concurrent with the upregulation of BCL2 protein compared with the parental H69 cell line and chemo-sensitive patients （P〈0.001）. miR-181d expression in H69 cells resistant to chemotherapy drugs （ADM, DDP, and VP-16） was inhibited （P〈0.01）. Enforced miR-181d expression reduced the BCL2 protein level and sensitized H69AR cells to chemotherapy drugs （P〈0.01）. miR-181d expression was associated with tumor stage, sensitivity of chemotherapy, and survival time （all P〈0.001）. Patients with high miR-181d expression had longer overall survival and progress-free survival time com-pared with those with low miR-181d expression （P〈0.001）. Conclusion： miR-181d may play a role in the development of MDR in SCLC and may be a potential predictive factor for treatment efficacy.

关 键 词：小细胞肺癌 多药耐药 

分 类 号：R734.2[医药卫生—肿瘤]