运用Microarray方法探究人肺癌对紫杉醇的耐药机制

Differential gene expression profile in drug-resistant human lung cancer A549/taxol cells

目的本研究旨在通过Microarray方法从基因组表达水平探讨人肺腺癌A549细胞对紫杉醇(paclitaxel,又名taxol)耐药的机制。方法生存曲线检测紫杉醇对人肺腺癌A549细胞株和耐紫杉醇的人肺腺癌A549细胞株(A549/taxol)治疗效果。Microarray方法检测A549与A549/taxol基因组表达水平的差异。结果生存曲线结果显示,在相同的治疗方案下分别移植A549与A549/taxol的两组小鼠模型的存活时间相差25天(P<0.01)。通过Microarray分析显示,与亲代A549细胞基因组表达水平比较,耐药性A549细胞基因组变化>3倍的约278个基因,其中163个基因表达水平上调,有115个基因表达水平下调(P<0.05)。结论细胞内基因组表达水平的差异可能是A549/taxol细胞对紫杉醇耐药的机制之一。

Objective To investigate the differential gene expression profile of paclitaxel（ taxol）-resistant human lung adenocarcinoma A549 cells. Methods The effect of taxol on human lung adenocarcinoma A549 cells and drugresistant A549 /taxol cells was determined by Kaplan-Meier survival curve. The differential gene expression of A549 and A549 /taxol cells was examined by microarray assay. Results The Kaplan-Meier curve showed that mice injected with A549 cells lived 25 days longer than the group injected with A549 /taxol cells with the same taxol-based program（ P 〈0. 01）. Genome-wide expression in these cells revealed that overall 163 and 115 genes were upregulated or downregulated 〉3 folds,respectively,in A549 /taxol cells. Conclusion The difference in genomic expression may be one of the mechanisms of taxol resistance in A549 /taxol cells.