表达谱芯片筛查非小细胞肺癌细胞系A549放疗抵抗差异基因

Differential expression profiles of mRNA in radioresistant non-small cell lung cancer cell line A549 model using gene expression microarray

目的建立非小细胞肺癌(NSCLC)A549放疗抵抗模型,表达谱芯片技术筛查放疗抵抗差异基因。方法 A549细胞系长期间歇照射诱导建立的放疗抵抗细胞模型;表达谱基因芯片筛查放疗抵抗细胞株与敏感株全基因组RNA表达差异;分析2倍以上差异的基因(P<0.05),分别进行生物学信息基因分类(GO)和信息通路(Pathway)分析。结果表达谱芯片显示,抵抗株与敏感株相比,差异表达基因为1410个(733个上调,677个下调);GO分析显示,主要与细胞周期、DNA修复有关;通路显著性富集分析显示,丝裂原活化蛋白激酶(MAPK)和磷脂酰肌醇-3-激酶(PI3K)等多条信号通路激酶出现显著性差异。结论多种基因和信号通路参与了放疗抵抗过程。

Objective To investigate the radioresistance factors in non-small cell lung cancer(NSCLC)cell line A549, and provide new targets for radiotherapy sensitization drugs development. Methods Establish the stable model of radioresistant NSCLC cell line A549 under irradiation;investigate the whole-transcriptome alteration of radioresistance cell line and radiosensitive cell line using gene expression microarray;perform bioinformatic approaches gene ontology(GO) analysis and Pathway analysis. Results The expression profile microarray showed that 1410 differentially expressed genes(733 up-regulated and 677 down-regulated) were detected in resistant and sensitive strains;GO analysis showed that it was mainly related to cell cycle and DNA replication;Pathway significant enrichment analysis showed that mitogen-activated protein kiase(MAPK) signaling pathway, phosphatidylinositol 3-kinase/protein kinase B(PI3 K/Akt) signaling pathway, were mainly associated with radioresistance. Conclusion Multiple genes and signaling pathways are involved in radioresistance, further studies are needed to investigate the radioresistance factors, which could provide new targets for radiotherapy sensitization drugs development.