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.

中文翻译：

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辛伐他汀可有效杀死放射抗性乳腺癌细胞。


背景他汀类药物是小分子3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂，广泛用于降低脂质代谢紊乱中的胆固醇水平。最近的临床前和临床研究表明，他汀类药物通过提高无复发生存率在乳腺癌治疗中发挥有益作用。不幸的是，潜在的机制仍然难以捉摸。材料和方法 辛伐他汀是最广泛使用的亲脂性他汀类药物之一，用于研究潜在的放射增敏作用以及对放射抗性乳腺癌细胞系中细胞存活和迁移的影响。结果 与亲本细胞对应物相比，放射抗性 MDA-MB-231-RR、T47D-RR 和 Au565-RR 细胞的特点是 3-羟基-3-甲基戊二酰辅酶 A 还原酶 (HMGCR) 表达上调，并伴有上皮间质细胞损伤。过渡（EMT）激活。辛伐他汀可以通过调动多种参与细胞凋亡和自噬的途径来杀死放射抗性乳腺癌细胞。在辛伐他汀存在的情况下，迁移能力和波形蛋白表达减弱，而 E-钙粘蛋白表达增加。结论本研究表明辛伐他汀可以有效地根除放射抗性乳腺癌细胞并减少其间质表型。