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Published on: June 17, 2014
Simvastatin modulates β-catenin/MDR1 expression on spheres derived from CF41.Mg canine mammary carcinoma cells
P Cruz1,2, F Reyes1, C G Torres1
1Laboratory of Biomedicine and Regenerative Medicine, Department of Clinical Sciences, Faculty of Veterinary and Animal Sciences, University of Chile, Santa Rosa Avenue 11735, La Pintana, 8820808 Chile.
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/β-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 β-catenin/MDR1 expression in spheres obtained from the CF41.Mg cell line as a model of CSC. Simvastatin increased phosphorylation of β-catenin without affecting its total expression. Moreover, MDR1 expression was decreased by simvastatin. These results suggest that simvastatin would facilitate the degradation of β-catenin, decreasing MDR1 expression and contributing to the chemosensitizing effects of the statin on canine mammary CSC.
Insights
Simvastatin reduces chemoresistance in canine mammary cancer stem cells (CSCs) by targeting the Wnt/β-catenin pathway. This drug decreases multidrug resistance protein 1 (MDR1) expression, enhancing treatment effectiveness.
Area of Science:
- Veterinary Oncology
- Cancer Stem Cell Biology
- Pharmacology
Background:
- Cancer stem-like cells (CSCs) in canine mammary tumors contribute to treatment resistance and recurrence.
- The Wnt/β-catenin pathway is often activated in CSCs, leading to multidrug resistance protein 1 (MDR1) upregulation and chemoresistance.
Purpose of the Study:
- To investigate the effect of simvastatin on β-catenin and MDR1 expression in canine mammary CSCs.
- To understand the mechanism by which simvastatin may overcome chemoresistance in these cells.
Main Methods:
- Utilized CF41.Mg canine mammary carcinoma cell line to generate CSC spheres.
- Analyzed the expression and phosphorylation of β-catenin and the expression of MDR1 following simvastatin treatment.
Main Results:
- Simvastatin treatment increased β-catenin phosphorylation but did not alter its total expression.
- Simvastatin significantly decreased the expression of MDR1 in canine mammary CSCs.
Conclusions:
- Simvastatin appears to promote β-catenin degradation, leading to reduced MDR1 expression.
- These findings suggest simvastatin has potential as a chemosensitizing agent for canine mammary CSCs, offering a new therapeutic avenue.
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