22 February 2018 : Laboratory Research
Downregulation of HIF-2α Reverse the Chemotherapy Resistance of Lung Adenocarcinoma A549 Cells to Cisplatin
Zhao-jia Gao12BCEF, Wei-dong Yuan1CD, Jun-qiang Yuan1CD, Kai Yuan12ACDFG*, Yong Wang1CDEDOI: 10.12659/MSM.906107
Med Sci Monit 2018; 24: LBR1104-1111
Abstract
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 14~40%. HIF-2α can upregulate drug-resistant-related genes expression and lead to chemotherapy resistance in many tumors. However, little is known about the relationship between HIF-2α and chemotherapy resistance of lung cancer cells.
MATERIAL AND METHODS: In our study, the siRNA expression vectors targeting the HIF-2α 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-2α gene silencing on the A549 cells in the cisplatin-based chemotherapy resistance.
RESULTS: After transfection with the siRNAHIF-2α into A549 cells, mRNA and protein expression of HIF-2α 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-2α and P-gp, which then can reverse the chemotherapy resistance of A549 cells.
Keywords: Cell Hypoxia, Drug Therapy, P-Glycoprotein
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