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

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/-catenin signaling pathway, which plays an important role in ovarian cancer. Peroxisome proliferator-activated receptor (PPAR) ligands have been found to protect against development of cancer through the Wnt/-catenin pathway. To investigate the effect of PPAR 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 PPAR ligands. Rosi downregulated FZD1 and MDR1/P-gp expression in a concentration-dependent manner. In addition, nuclear -catenin levels and its transcriptional activity decreased significantly. In conclusion, Rosi may reverse MDR of ovarian cancer cells by downregulating the Wnt/-catenin pathway with the suppression of FZD1.