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Simvastatin is effective in killing the radioresistant breast carcinoma cells.

Medical University of Innsbruck, Therapeutic Radiology and Oncology, Innsbruck, Austria. Tyrolean Cancer Research Institute, Innsbruck, Austria. EORTC PathoBiology Group Moscow, Russia. Institute of Personalized Medicine, Sechenov First Moscow State Medical University, Moscow, Russia. Omicsway Corp., Walnut, USA. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia. Oncobox ltd., Moscow, Russia. World-Class Research Center "Digital Biodesign and Personalized Healthcare", Sechenov First Moscow State Medical University, Moscow, Russia. Institute of Oncology Ljubljana, Department of Experimental Oncology, Ljubljana, Slovenia.

Radiology and oncology. 2021;(3):305-316
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Abstract

BACKGROUND Statins, small molecular 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, are widely used to lower cholesterol levels in lipid-metabolism disorders. Recent preclinical and clinical studies have shown that statins exert beneficial effects in the management of breast cancer by increasing recurrence free survival. Unfortunately, the underlying mechanisms remain elusive. MATERIALS AND METHODS Simvastatin, one of the most widely prescribed lipophilic statins was utilized to investigate potential radiosensitizing effects and an impact on cell survival and migration in radioresistant breast cancer cell lines. RESULTS Compared to parental cell counterparts, radioresistant MDA-MB-231-RR, T47D-RR andAu565-RR cells were characterized by upregulation of 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMGCR) expression accompanied by epithelial-to-mesenchymal transition (EMT) activation. Radioresistant breast cancer cells can be killed by simvastatin via mobilizing of a variety of pathways involved in apoptosis and autophagy. In the presence of simvastatin migratory abilities and vimentin expression is diminished while E-cadherin expression is increased. CONCLUSIONS The present study suggests that simvastatin may effectively eradicate radioresistant breast carcinoma cells and diminish their mesenchymal phenotypes.