Relationship between HIF-2α Gene and Chemotherapy Resistance of Lung Adenocarcinoma A549 Cells to Cisplatin

Objective:To investigate the effect of silencing hypoxia inducible factor-2 alpha(HIF-2α)gene expression by small interfering RNA(siRNA)on chemotherapy resistance of A549 cells to cisplatin.Methods:The siRNA eukaryotic expression vectors targeting HIF-2αgene were constructed and transfected into A549 cells.The expression of HIF-2αmRNA was detected by real-time PCR.The expression of HIF-2αand multidrug resistance-1(Mdr-1)proteins were detected by Western blotting. MTT assay was used to explore the survival rate of A549 cells under the treatment of cisplatin.Results:After transfection of HIF-2αsiRNA into A549 cells for 24 and 48 h,the expression levels of HIF-2αmRNA and protein were both down-regulated significantly compared with those in the blank group(all P0.01).Meanwhile,the protein expression level of Mdr-1 also decreased significantly(all P0.05).The sensitivity of A549 cells to cisplatin was significantly increased in HIF-2αsiRNA transfection group compared with that in the blank group.The IC50 value at each time point was significantly decreased,and the difference was statistically significant(all P0.01).Conclusions:The siRNA expression vector targeting HIF-2αconstructed in this study can effectively inhibit the expression of HIF-2αgene,and thus reversing the chemotherapy resistance of A549 cells to cisplatin.