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非小细胞肺癌耐药细胞株A549/DDP中microRNA表达的初步研究 被引量:23

Analysis of microRNAs in drug-resistant NSCLC cell line A549/DDP
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摘要 目的:应用mi RNA芯片技术检测非小细胞肺癌(NSCLC)细胞株A549及顺铂(DDP)耐药株A549/DDP miRNAs表达的差异。方法:MTT法检测A549/DDP相对于其亲本细胞A549的耐药性和耐药倍数;分别提取2种细胞的总RNA进行质检;microRNA芯片检测NSCLC细胞株A549及对应的DDP耐药株A549/DDP中mi RNA表达差异;采用real-ti me PCR验证结果。结果:DDP对A549和A549/DDP细胞的IC50值分别为7.47和137.32μmol/L,两者差异有统计学意义(P〈0.01),耐药倍数为18.38倍。microR-NA芯片结果显示,耐药株A549/DDP与亲本细胞系A549比较有34条有差异表达的miR-NA(19条上调,15条下调)差异比值〉1.5倍或〈0.67倍,P〈0.05;real-ti me PCR的结果进一步证实miR-21、miR-31和miR-374在A549/DDP中显著上调,而miR-378、miR-886-5p、miR-886-3p和miR-520c-3p在A549/DDP中显著下调。结论:A549/DDP与A549的miRNA的表达谱存在差异,miRNA可能参与NSCLC DDP耐药,为进一步研究miRNA在NSCLC DDP耐药机制中的作用奠定基础。 OBJECTIVE:To analyze the difference in miRNAs expression between A549 and A549/DDP cells and explore the association between miRNA and cisplatin resistanc of non-small cell lung cancer(NSCLC).METHODS:The drug resistance of A549/DDP cells was evaluated by using MTT assay.The total RNA of the two cell lines was isolated and examined.The miRNA expressions of A549/DDP and A549 were analyzed by using microarray and the results were confirmed by real-time PCR.RESULTS:The values of IC50 of cisplatin to A549 cells and A549/DDP cells were 7.47 and 137.32 μmol/L respectively(P0.01).The drug resistance index of A549/DDP cells relative to the parental A549 cells was 18.38.The microarray analysis showed that 34 human miRNAs were differentially expressed between two cell lines(Fold change1.5 or0.67,and P0.05).Compared to A549 cells,there were 19 miRNAs up-regulated and 15 miRNAs down-regulated in A549/DDP,Among the differentially expressed miRNAs,miR-21,miR-31 and miR-374 were upregulated and miR-378,miR-886-5P,miR-886-3P were downregulated,whose expression was further validated by red time PCR.CONCLUSIONS:NSCLC resistant to cisplatin is associated with a group of miRNAs.This finding provides an experimental basis for further study of mechanism underlying the cisplatin resistance of NSCLC.
作者 陆晓 孙婧 高雯 徐小涛 束永前 LU Xiao,SUN Jing,GAO Wen,XU Xiao-tao,SHU Yong-qian Department of Oncology,First Affliated Hospital of Nanjing Medical University,Nanjing 210029,P.R.China
出处 《中华肿瘤防治杂志》 CAS 2010年第9期659-663,共5页 Chinese Journal of Cancer Prevention and Treatment
基金 江苏省医学重点学科项目(XK200718)
关键词 非小细胞肺 顺铂 抗药性 肿瘤 芯片 MICRORNA carcinoma non-small-cell lung cisplatin drug resistance neoplasm microarray microRNA
作者简介 陆晓,女,江苏常熟人,硕士,主要从事肺癌化疗耐药的基础研究工作。Tel:86—25—68136043 E-mail:luxiao1228@sina.com 【通讯作者简介】束永前,男,江苏苏州人,教授,博士生导师,主要从事肺癌的早期诊断、个体化治疗、靶向治疗及预后因素分析的基础及临床研究工作。rrel:86—25—83718836—6428 E-mail:shuyongqian@csco.org.cn
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