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Interference of Frizzled 1 (FZD1) Reverses Multidrug Resistance in Breast Cancer Cells through the Wnt/beta-Catenin Pathway

By: Zhang H, Zhang X, Wu X, Li W, Su P, Cheng H, Xiang L, Gao P, Zhou G.

Department of Pathology and Pathophysiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
Cancer Lett. 2012 Apr 4.

Abstract

Multidrug resistance (MDR) represents a major obstacle in the successful treatment of breast cancer. The MDR1 gene is a direct target of the Wnt/β-catenin signaling pathway, which controls tumor development. Overexpression of P-glycoprotein, encoded by the MDR1 gene, is one of the most common causes of MDR. We found that the Frizzled 1 (FZD1) protein, which is an essential component of the Wnt/β-catenin pathway, is overexpressed in the multidrug resistant breast cancer cell subline MCF-7/ADM, coincident with MDR1/P-gp. FZD1 silencing induced down-regulation of MDR1/P-gp, restored sensitivity to four chemotherapy drugs, and significantly decreased cytoplasmic and nuclear β-catenin levels. FZD1 appears to mediate multidrug resistance by regulating the Wnt/β-catenin pathway.

PMID: 22484497 [PubMed - as supplied by publisher] Source: National Library of Medicine.