背景与目的肿瘤干细胞可能是肿瘤多药耐药的主要原因，CD133是目前较为公认的肿瘤干细胞标记物。本研究旨在应用功能分类基因芯片筛选CD133+和CD133-肺腺癌细胞中差异表达的肿瘤耐药基因，寻求新的肺癌耐药相关基因。方法免疫磁珠分选法分选A549细胞，采用功能分类基因芯片筛选CD133+和CD133-肺腺癌细胞中差异表达的肿瘤耐药基因，并使用RT-qPCR验证。顺铂半数有效抑制浓度（half inhibiting concentration, IC50）、阿霉素IC50作用A549细胞48 h后，RT-qPCR检测肿瘤耐药基因CYP2C19、CYP2D6、CYP2E1、GSK3α、PPARα和PPARβ/δ的表达变化。结果共筛查出31个差异表达的肿瘤耐药基因，与CD133-细胞相比，CD133+细胞有30个基因表达上调，1个基因表达下调。RT-qPCR结果与芯片一致。A549细胞经1.97μg/mL顺铂或0.61μg/mL阿霉素作用48 h后，CYP2C19、CYP2D6、CYP2E1、GSK3α、PPARα和PPARβ/δ等肿瘤耐药基因表达上调。结论利用功能分类基因芯片筛选出31个可能与CD133+肺腺癌细胞耐药相关的基因，其中CYP2C19、CYP2D6、CYP2E1、GSK3α、PPARα和PPARβ/δ为新发现的肺癌耐药相关基因。%Background and objective Cancer stem cells (CSCs) are responsible for multi-drug resistance in tu-mors. CD133 is a known biomarker of CSCs. hTe aim of this study is to screen for drug-resistant differentially expressed genes in CD133+and CD133-lung cancer cells and to identify novel lung tumor drug-resistant genes. Methods Magnetic activated cell sorting was used to isolate CD133+and CD133-cells from human lung cancer cell line A549, and drug-resistant microarray was used to detect drug-resistant genes in the these cells. RT-qPCR was used to examine the expression of six lung tumor drug-resistant genes in pre-and post-chemotherapeutic A549 cells. Results A total of 31 differentially expressed genes were screened by microar-ray analysis. Of these genes, 30 were upregulated and one was downregulated in CD133+cells compared with CD133-cells. Re-sults were veriifed by RT-qPCR. CYP2C19, CYP2D6, CYP2E1, GSK3α, PPARα, and PPARβ/δwere signiifcantly upregulated atfer the A549 cells were treated with 1.97μg/mL DDP or 0.61μg/mL doxorubicin for 48 h. Conclusion hTe drug resistance of lung adenosarcoma may be correlated with 31 differentially expressed genes screened by drug-resistant microarray. CYP2C19, CYP2D6, CYP2E1, GSK3α, PPARα, and PPARβ/δmight be novel lung adenosarcoma drug-resistant genes.
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