Medical University of Innsbruck, Therapeutic Radiology and Oncology, Innsbruck, Austria.
Tyrolean Cancer Research Institute, Innsbruck, Austria.
Radiol Oncol. 2021 May 4;55(3):305-316. doi: 10.2478/raon-2021-0020.
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.
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.
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.
The present study suggests that simvastatin may effectively eradicate radioresistant breast carcinoma cells and diminish their mesenchymal phenotypes.
他汀类药物，即小分子 3-羟基-3-甲基戊二酰辅酶 A 还原酶抑制剂，被广泛用于降低脂代谢紊乱患者的胆固醇水平。最近的临床前和临床研究表明，他汀类药物通过增加无复发生存率，在乳腺癌的治疗中发挥有益作用。不幸的是，其潜在机制仍难以捉摸。
利用最广泛使用的亲脂性他汀类药物辛伐他汀，来研究其在放射抗性乳腺癌细胞系中潜在的放射增敏作用以及对细胞存活和迁移的影响。
与亲本细胞相比，放射抗性 MDA-MB-231-RR、T47D-RR 和 Au565-RR 细胞表现出 3-羟基-3-甲基戊二酰辅酶 A 还原酶（HMGCR）表达上调，伴有上皮间质转化（EMT）激活。辛伐他汀可通过激活多种涉及细胞凋亡和自噬的途径杀死放射抗性乳腺癌细胞。在辛伐他汀的存在下，迁移能力降低，波形蛋白表达减少，而 E-钙黏蛋白表达增加。
本研究表明，辛伐他汀可能有效根除放射抗性乳腺癌细胞，并减少其间充质表型。
