miR-21 modulates paclitaxel sensitivity and hypoxia-inducible factor-1α expression in human ovarian cancer cells

Abstract

Drug resistance is a major problem encountered in the treatment of ovarian cancer. Previous studies have demonstrated that in several types of cancer the overexpression of the multidrug resistance 1 (MDR1) gene is mainly associated with drug resistance. The present study aimed to investigate the role of miR‑21 in the development of drug resistance in ovarian cancer cells. The expression levels of miR‑21 in the ovarian cancer A2780 and A2780/taxol cell lines were detected by stem‑loop real‑time PCR. A2780 and A2780/taxol cells were transfected with mimics or inhibitors of miR‑21 or negative control RNA. The expression levels of P‑glycoprotein (P‑gp) and hypoxia‑inducible factor‑1α (HIF‑1α) proteins were assessed by western blot analysis. Drug sensitivity was analyzed by the 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) assay. The expression levels of miR‑21 and P‑gp were upregulated to a greater extent in the paclitaxel‑resistant ovarian cancer A2780/taxol cell line compared with the parental A2780 cell line. Transfection of A2780/taxol cells with inhibitors of miR‑21 decreased the expression levels of the P‑gp and HIF‑1α proteins, and increased the sensitivity of the A2780/taxol cells to paclitaxel. The expression levels of P‑gp were additionally increased; however, the sensitivity of the miR‑21 mimic‑treated A2780 cells to paclitaxel was decreased. miR‑21 may be involved in the development of drug resistance and the regulation of MDR1/P‑gp expression, at least in part, by targeting HIF‑1α in ovarian cancer cells.