Simvastatin is effective in killing the radioresistant breast carcinoma cells
Article Category: Research Article
Online veröffentlicht: 04. Mai 2021
Seitenbereich: 305 - 316
Eingereicht: 10. März 2021
Akzeptiert: 02. Apr. 2021
DOI: https://doi.org/10.2478/raon-2021-0020
© 2021 Bertram Aschenbrenner, Giulia Negro, Dragana Savic, Maxim Sorokin, Anton Buzdin, Ute Ganswindt, Maja Cemazar, Gregor Sersa, Sergej Skvortsov, Ira Skvortsova, published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
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.