Suppression of multidrug resistance by rosiglitazone treatment in human ovarian cancer cells through downregulation of FZD1 and MDR1 genes.

Suppression of multidrug resistance by rosiglitazone treatment in human ovarian cancer cells through downregulation of FZD1 and MDR1 genes.

Anticancer Drugs. 2015 Jun 5;

Authors: Zhang H, Jing X, Wu X, Hu J, Zhang X, Wang X, Su P, Li W, Zhou G

Abstract
Multidrug resistance (MDR) is a major obstacle in the successful treatment of ovarian cancer. One of the most common causes of MDR is overexpression of P-glycoprotein (P-gp), encoded by the MDR1 gene. The MDR1 gene is a direct target of the Wnt/β-catenin signaling pathway, which plays an important role in ovarian cancer. Peroxisome proliferator-activated receptor γ (PPARγ) ligands have been found to protect against development of cancer through the Wnt/β-catenin pathway. To investigate the effect of PPARγ ligands on MDR1/P-gp expression, we treated a MDR ovarian cancer cell subline, A2780/Taxol, with different concentrations of rosiglitazone (Rosi), a member of the synthetic PPARγ ligands. Rosi downregulated FZD1 and MDR1/P-gp expression in a concentration-dependent manner. In addition, nuclear β-catenin levels and its transcriptional activity decreased significantly. In conclusion, Rosi may reverse MDR of ovarian cancer cells by downregulating the Wnt/β-catenin pathway with the suppression of FZD1.

PMID: 26053275 [PubMed - as supplied by publisher]