Wang Hongyan, Zheng Shaoqiu, Tu Yongsheng, Zhang Yajie
Department of Pathology, Guangzhou Medical University, Guangzhou 510182, China.
Department of Physiology, Guangzhou Medical University, Guangzhou 510182, China.
Zhongguo Fei Ai Za Zhi. 2014 Jun 20;17(6):437-43. doi: 10.3779/j.issn.1009-3419.2014.06.01.
Cancer stem cells (CSCs) are responsible for multi-drug resistance in tumors. CD133 is a known biomarker of CSCs. The 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.
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.
A total of 31 differentially expressed genes were screened by microarray analysis. Of these genes, 30 were upregulated and one was downregulated in CD133+ cells compared with CD133- cells. Results were verified by RT-qPCR. CYP2C19, CYP2D6, CYP2E1, GSK3α, PPARα, and PPARβ/δ were significantly upregulated after the A549 cells were treated with 1.97 μg/mL DDP or 0.61 μg/mL doxorubicin for 48 h.
The 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/δ might be novel lung adenosarcoma drug-resistant genes.
癌症干细胞(CSCs)是肿瘤多药耐药的原因。CD133是已知的癌症干细胞生物标志物。本研究旨在筛选CD133 +和CD133 -肺癌细胞中的耐药差异表达基因,并鉴定新的肺肿瘤耐药基因。
采用磁激活细胞分选技术从人肺癌细胞系A549中分离CD133 +和CD133 -细胞,并使用耐药基因芯片检测这些细胞中的耐药基因。采用RT-qPCR检测化疗前后A549细胞中六个肺肿瘤耐药基因的表达。
通过基因芯片分析共筛选出31个差异表达基因。与CD133 -细胞相比,这些基因中有30个在CD133 +细胞中上调,1个下调。结果通过RT-qPCR验证。用1.97μg/mL顺铂或0.61μg/mL阿霉素处理A549细胞48小时后,CYP2C19、CYP2D6、CYP2E1、GSK3α、PPARα和PPARβ/δ显著上调。
肺腺肉瘤的耐药性可能与耐药基因芯片筛选出的31个差异表达基因有关。CYP2C19、CYP2D6、CYP2E1、GSK3α、PPARα和PPARβ/δ可能是新的肺腺肉瘤耐药基因。