Hypoxia-induced increases in A549/CDDP cell drug resistance are reversed by RNA interference of HIF-1α expression

Abstract

This study aimed to investigate the effects of knocking down hypoxia-inducible factor-1α (HIF-1α) through RNA interference on hypoxia-induced increases in drug resistance in A549/CDDP cells, and to study the underlying mechanisms. A small interfering RNA (siRNA) eukaryotic expression vector targeting HIF-1α was constructed and transfected into A549/CDDP cells treated with hypoxia. The mRNA and protein levels of HIF-1α, multidrug resistance-1 (MDR1), and multidrug resistance-associated protein (MRP) were determined by reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemistry. Cell viability following treatment with cisplatin was determined by MTT assay. Hypoxia increased the resistance of A549/CDDP cells to cisplatin and this effect was reversed by the siRNA inhibition of HIF-1α expression. Expression of HIF-1α siRNA also downregulated HIF-1α, MDR1 and MRP mRNA, and protein expression in A549/CDDP cells treated with hypoxia (p<0.05). Hypoxia-induced resistance of A549/CDDP cells to cisplatin is reversed by the siRNA inhibition of HIF-1α expression. This effect may be mediated by a decreased expression of MDR1 and MRP.