Mannello Ferdinando, Tonti Gaetana A
Department of Biomolecular Sciences, Section of Clinical Biochemistry, University Carlo Bo, Urbino, Italy.
Cancer Invest. 2009 May;27(4):466-70. doi: 10.1080/07357900802491444.
Statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors), cholesterol-lowering agents widely prescribed for cardiovascular health, have been shown to exert several pleiotropic effects. Although some studies reported that statins have no effects on malignancies of any kind, results of several epidemiologic and in vitro studies highlighted that statins exert anticancer activity in various cell types, showing that long-term therapy inhibits the incidence and/or progression of some human tumours. In particular, in the present overview we focused the attention on a neglected aspect of the pleiotropic functions of some lipophilic statins, suggesting that the possible mechanism of matrix metalloproteinase downregulation arises from prolonged lowering of circulating cholesterol. Our hypothesis may explain the literary findings about the phenomenon of switching of breast cancer phenotypes by statins, shedding the basis of future epidemiologic and basic science studies about the role of circulating and/or tumor-resident cholesterol in the initiation and progression of breast cancer.
他汀类药物（3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂）是广泛用于心血管健康的降胆固醇药物，已被证明具有多种多效性作用。尽管一些研究报告称他汀类药物对任何类型的恶性肿瘤均无影响，但多项流行病学和体外研究结果表明，他汀类药物在多种细胞类型中具有抗癌活性，表明长期治疗可抑制某些人类肿瘤的发生和/或进展。特别是，在本综述中，我们将注意力集中在一些亲脂性他汀类药物多效性功能中一个被忽视的方面，表明基质金属蛋白酶下调的可能机制源于循环胆固醇的长期降低。我们的假设可能解释了关于他汀类药物改变乳腺癌表型现象的文献研究结果，为未来关于循环和/或肿瘤内胆固醇在乳腺癌发生和进展中的作用的流行病学和基础科学研究奠定了基础。
