miR-135a在调节小细胞肺癌多药耐药中的作用  

The role of miR-135a in regulating multi-drug resistance of small cell lung cancer

作　　者：苏文媚[1] 林燕明[1] 罗亮[1] 梁亚海[1] 刘美莲[1] 赖振南[1] 杨志雄[1] 梁荣[1] 

机构地区：[1]广东医学院附属医院肿瘤中心,广东湛江524000

出　　处：《中国肿瘤生物治疗杂志》2015年第3期304-309,共6页Chinese Journal of Cancer Biotherapy

基　　金：广东省医学科研基金(No.B2014310)~~

摘　　要：目的:探讨miR-135a在小细胞肺癌(small cell lung cancer,SCLC)多药耐药中的作用。方法:收集2008年1月至2013年12月本院肿瘤科及呼吸内科就诊的48例SCLC患者外周血液标本,将其分为化疗敏感组(28例)和耐药组(20例),采用QRT-PCR法检测患者血液标本、SCLC敏感细胞株H69及耐药细胞株H69AR中miR-135a的表达,分析其与临床预后的关系,并应用miR-135a模拟物和抑制剂分别上、下调细胞株中miR-135a的表达,采用CCK-8法检测细胞对各种化疗药物(ADM、DDP和VP-16)敏感性的影响。结果:与化疗敏感组相比,miR-135a在化疗耐药患者血液标本中的表达明显增高[(2.174±3.981)vs(-1.963±3.750),P<0.001];在临床患者血液标本中,miR-135a的表达与患者的性别、年龄无关(P>0.05),与疾病的分期、化疗敏感性及患者的生存时间相关(均P<0.01)。miR-135a在H69AR细胞中的表达明显高于H69细胞[(7.841±0.392)vs(1.047±0.081),P<0.01];通过miR-135a抑制剂下调H69AR中miR-135a的表达能够显著增加细胞对化疗药物的敏感性,H69AR细胞对DDP、ADM及VP-16的IC50值明显下降[(247.09±11.55)vs(76.64±10.00)、(150.83±8.03)vs(40.72±5.06)、(436.63±61.19)vs(163.35±20.00);H69细胞转染miR-135a mimics后对化疗药物DDP、ADM和VP-16的IC50值明显增加[(18.58±1.37)vs(159.27±3.29)、(24.37±2.63)vs(129.19±2.64),(48.55±2.59)vs(359.87±2.92)μg/ml,P<0.01]。结论:miR-135a参与调节SCLC的多药耐药,下调miR-135a基因的表达可能增加细胞对化疗药物的敏感性。Objective: To investigate the role of miR-135 a in regulating multi-drug resistance of small cell lung cancer.Methods: The expression of miR-135 a was assessed by qRT-PCR in peripheral blood samples collected from 48 patients with SCLC admitted to our department between Janurary 2008 and December 2013,which include both chemotherapy responders( 28 patients) and non-responders( 20 patients). The relationships between miR-135 a expression and treatment response,clinical pathological features,and prognosis of patients were analyzed. We also determined the expression of miR-135 a in the drug-sensitive SCLC H69 cells and drug-resistant H69 AR cell line by qRT-PCR and examined the effects of miR-135 a mimics and inhibitor on the sensitivities of H69 and H69 AR to chemotherapy drugs ADM,DDP,VP-16 by CCK-8 assay. Results: The level of miR-135 a was significantly increased in SCLC non-responders compared with that in the responders [( 2. 174 ± 3. 981) vs(- 1. 963 ± 3. 750),P < 0. 001]. While it is not correlated with gender and age of the patients( P > 0. 05),miR-135 a level is statistically correlated with clinical stage,chemosensitivity and overall survival( all P < 0. 05). The expression of miR-135 a was also markedly increased in H69 AR cells compared with that in the H69 cells [( 7. 841 ± 0. 392) vs( 1. 047 ± 0. 081),P < 0. 01]. The drug-sensitivities H69 cells became more resistant to chemotherapeutics DDP,ADM and VP-16 after transfected with miR-135 a mimics,and exhibited significantly increased IC50[( 18. 58 ± 1. 37) vs( 159. 27 ± 3. 29),( 24. 37 ± 2. 63) vs( 129. 19 ± 2. 64),and( 48. 55 ± 2. 59) vs( 359. 87 ± 2. 92)μg /ml,all P < 0. 01]. Furthermore,the drug-resistant H69 AR cells became more sensitive to these drugs when miR135 a was downregulated,and had markedly decreased IC50[( 247. 09 ± 11. 55) vs( 76. 64 ± 10. 00),( 150. 83 ± 8. 03) vs( 40.72 ± 5. 06),( 436. 63 ± 61. 19) vs( 163. 35 ± 20. 00) μg / ml; all P < 0. 01]. Conclusion: In small cell lung cancer,miR-135 a participates in the regul

关 键 词：小细胞肺癌 miR-135a 多药耐药 

分 类 号：R734.2[医药卫生—肿瘤]