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Published on: March 30, 2019
[Screening and identification of novel drug-resistant genes in CD133+ and CD133- lung adenosarcoma cells using cDNA
Hongyan Wang1, Shaoqiu Zheng1, Yongsheng Tu2
1Department of Pathology, Guangzhou Medical University, Guangzhou 510182, China.
Background:
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.
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 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.
Conclusions:
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.
Insights
This study identified 31 differentially expressed genes in CD133+ lung cancer cells, including potential novel drug-resistant genes like CYP2C19 and PPARα. These findings may help overcome multi-drug resistance in lung adenocarcinoma.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Cancer stem cells (CSCs) drive multi-drug resistance in tumors.
- CD133 is a recognized biomarker for CSCs.
- Understanding drug resistance mechanisms in lung cancer is crucial.
Purpose of the Study:
- To screen for differentially expressed genes related to drug resistance in CD133+ and CD133- lung cancer cells.
- To identify novel genes contributing to drug resistance in lung tumors.
- To investigate the role of specific genes in lung adenosarcoma drug resistance.
Main Methods:
- Magnetic activated cell sorting to isolate CD133+ and CD133- cells from A549 lung cancer cell line.
- Drug-resistant microarray analysis to detect differentially expressed genes.
- RT-qPCR to validate gene expression and examine specific drug-resistant genes pre- and post-chemotherapy.
Main Results:
- Microarray analysis identified 31 differentially expressed genes between CD133+ and CD133- cells (30 upregulated, 1 downregulated).
- RT-qPCR confirmed the differential expression and validated upregulation of CYP2C19, CYP2D6, CYP2E1, GSK3α, PPARα, and PPARβ/δ post-chemotherapy treatment.
- Significant upregulation of these six genes was observed after treatment with DDP or doxorubicin.
Conclusions:
- The 31 differentially expressed genes identified may be associated with the drug resistance of lung adenosarcoma.
- CYP2C19, CYP2D6, CYP2E1, GSK3α, PPARα, and PPARβ/δ are proposed as novel potential drug-resistant genes in lung adenosarcoma.
- These findings provide insights into molecular mechanisms of drug resistance and potential therapeutic targets.

