Department of Pharmaceutical and Biomedical Sciences, University of Salerno, Via Ponte Don Melillo, 84084 Fisciano (Salerno), Italy.
Pharmacol Rev. 2012 Jan;64(1):102-46. doi: 10.1124/pr.111.004994. Epub 2011 Nov 21.
Statins, among the most commonly prescribed drugs worldwide, are cholesterol-lowering agents used to manage and prevent cardiovascular and coronary heart diseases. Recently, a multifaceted action in different physiological and pathological conditions has been also proposed for statins, beyond anti-inflammation and neuroprotection. Statins have been shown to act through cholesterol-dependent and -independent mechanisms and are able to affect several tissue functions and modulate specific signal transduction pathways that could account for statin pleiotropic effects. Typically, statins are prescribed in middle-aged or elderly patients in a therapeutic regimen covering a long life span during which metabolic processes, aging, and concomitant novel diseases, including cancer, could occur. In this context, safety, toxicity, interaction with other drugs, and the state of health have to be taken into account in subjects treated with statins. Some evidence has shown a dichotomous effect of statins with either cancer-inhibiting or -promoting effects. To date, clinical trials failed to demonstrate a reduced cancer occurrence in statin users and no sufficient data are available to define the long-term effects of statin use over a period of 10 years. Moreover, results from clinical trials performed to evaluate the therapeutic efficacy of statins in cancer did not suggest statin use as chemotherapeutic or adjuvant agents. Here, we reviewed the pharmacology of the statins, providing a comprehensive update of the current knowledge of their effects on tissues, biological processes, and pathological conditions, and we dissected the disappointing evidence on the possible future use of statin-based drugs in cancer therapy.
他汀类药物是全球最常用的处方药物之一，属于降胆固醇药物，用于治疗和预防心血管疾病和冠心病。最近，人们提出他汀类药物在多种生理和病理条件下具有多效性作用，除了抗炎和神经保护作用之外。他汀类药物被证明可以通过胆固醇依赖性和非依赖性机制发挥作用，能够影响几种组织功能，并调节特定的信号转导途径，这可以解释他汀类药物的多效性作用。通常，他汀类药物在中年或老年患者中开处方，治疗方案涵盖了很长的生命周期，在此期间可能会发生代谢过程、衰老和伴随的新疾病，包括癌症。在这种情况下，必须考虑接受他汀类药物治疗的患者的安全性、毒性、与其他药物的相互作用和健康状况。一些证据表明他汀类药物具有抑制或促进癌症的双重作用。迄今为止，临床试验未能证明他汀类药物使用者癌症发病率降低，也没有足够的数据来定义他汀类药物使用 10 年以上的长期效果。此外，为评估他汀类药物在癌症中的治疗效果而进行的临床试验结果并未表明他汀类药物可作为化疗或辅助药物使用。在这里，我们综述了他汀类药物的药理学，提供了对其在组织、生物学过程和病理条件下的作用的最新全面了解，并剖析了他汀类药物在癌症治疗中可能的未来用途的令人失望的证据。
