期刊
MEDICAL SCIENCE MONITOR
卷 24, 期 -, 页码 1104-1111出版社
INT SCIENTIFIC INFORMATION, INC
DOI: 10.12659/MSM.906107
关键词
Carcinoma, Non-Small-Cell Lung; Cell Hypoxia; Cisplatin; Drug Therapy; P-Glycoprotein
资金
- Basic Research Project of Changzhou [CJ20140041]
- High-Level Medical Talents Training Project [2016CZBJ042]
- Jiangsu Provincial Medical Youth Talent (Jiangsu Health Scientific Education) [3]
- Postdoctoral Program of Nanjing Medical University
Background: Cisplatin (DDP)-based systemic chemotherapy has been widely used in the treatment of postoperative or advanced NSCLC patients, however, its effective rate is only 14 similar to 40%. HIF-2 alpha can upregulate drug-resistant-related genes expression and lead to chemotherapy resistance in many tumors. However, little is known about the relationship between HIF-2 alpha and chemotherapy resistance of lung cancer cells. Material/Methods: In our study, the siRNA expression vectors targeting the HIF-2 alpha gene were designed, constructed, and transfected into A549 cells. MTT assay and western blot analysis of P-glycoprotein 1 (P-gp) were used to explore the transfer influence of HIF-2 alpha gene silencing on the A549 cells in the cisplatin-based chemotherapy resistance. Results: After transfection with the siRNA HIF-2 alpha into A549 cells, mRNA and protein expression of HIF-2 alpha were downregulated. At the same time, expression of P-gp decreased significantly. Furthermore, the sensitivity to cisplatin significantly increased. Conclusions: The constructed siRNA expression vectors can effectively suppress the expression of HIF-2 alpha and P-gp, which then can reverse the chemotherapy resistance of A549 cells.
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