Simvastatin modulates beta-catenin/MDR1 expression on spheres derived from CF41.Mg canine mammary carcinoma cells

Abstract

The presence of cancer stem-like cells (CSC) within canine mammary tumors, may explain partly local recurrence and spreading, since their ability to resist conventional antitumor treatments as chemo and radiotherapy. It has been recently described that simvastatin - a drug that inhibits synthesis of cholesterol - attenuates the proliferation of canine mammary CSC derived from CF41.Mg canine mammary carcinoma cells, promoting their chemosensitizing and apoptosis. The canonical Wnt/beta-catenin pathway is usually activated at CSC and up-regulates multidrug resistance protein 1 (MDR1), triggering chemoresistance. In the present study, we analyze the effect of simvastatin on beta-catenin/MDR1 expression in spheres obtained from the CF41.Mg cell line as a model of CSC. Simvastatin increased phosphorylation of beta-catenin without affecting its total expression. Moreover, MDR1 expression was decreased by simvastatin. These results suggest that simvastatin would facilitate the degradation of beta-catenin, decreasing MDR1 expression and contributing to the chemosensitizing effects of the statin on canine mammary CSC.