Ahmadi Yasin, Ghorbanihaghjo Amir, Argani Hassan
Tabriz University of Medical Sciences, Student Research Committee, Tabriz, Iran; Tabriz University of Medical Sciences, Biotechnology Research Center, Tabriz, Iran.
Tabriz University of Medical Sciences, Biotechnology Research Center, Tabriz, Iran.
Chem Biol Interact. 2017 Aug 1;273:273-285. doi: 10.1016/j.cbi.2017.06.026. Epub 2017 Jun 28.
Statins are widely used drugs for their role in decreasing cholesterol in hypercholesterolemic patients. Statins through inhibition of Hydroxy Methyl Glutaryl-CoA Reductase (HMGCR), the main enzyme of the cholesterol biosynthesis pathway, inhibit mevalonate pathway that provides isoprenoids for prenylation of different proteins such as Ras superfamily which has an essential role in cancer developing. Inhibition of the mevalonate/isoprenoid pathway is the cause of the cholesterol independent effects of statins or pleotropic effects. Depending on their penetrance into the extra-hepatic cells, statins have different effects on mevalonate/isoprenoid pathway. Lipophilic statins diffuse into all cells and hydrophilic ones use a variety of membrane transporters to gain access to cells other than hepatocytes. It has been suggested that the lower accessibility of statins for extra-hepatic tissues may result in the compensatory induction of mevalonate/isoprenoid pathway and so cancer developing. However, most of the population-based studies have demonstrated that statins have no effect on cancer developing, even decrease the risk of different types of cancer. In this review we focus on the cancer developing "potentials" and the anti-cancer "activities" of statins regarding the effects of statins on mevalonate/isoprenoid pathway in the liver and extra-hepatic tissues.
他汀类药物因其在降低高胆固醇血症患者胆固醇方面的作用而被广泛使用。他汀类药物通过抑制胆固醇生物合成途径的主要酶——羟甲基戊二酰辅酶A还原酶（HMGCR），抑制甲羟戊酸途径，该途径为不同蛋白质（如在癌症发展中起重要作用的Ras超家族）的异戊二烯化提供类异戊二烯。甲羟戊酸/类异戊二烯途径的抑制是他汀类药物非胆固醇依赖性作用或多效性作用的原因。根据他汀类药物对肝外细胞的渗透情况，它们对甲羟戊酸/类异戊二烯途径有不同的影响。亲脂性他汀类药物可扩散到所有细胞中，而亲水性他汀类药物则利用多种膜转运蛋白进入除肝细胞以外的其他细胞。有人认为，他汀类药物对肝外组织的可及性较低可能导致甲羟戊酸/类异戊二烯途径的代偿性诱导，从而引发癌症。然而，大多数基于人群的研究表明，他汀类药物对癌症发展没有影响，甚至会降低不同类型癌症的风险。在这篇综述中，我们将重点关注他汀类药物对肝脏和肝外组织中甲羟戊酸/类异戊二烯途径的影响，探讨他汀类药物的癌症发展“潜力”和抗癌“活性”。
