INSERM U1078-ECLA and SFR-ScInBioS, European University, Bretagne, France.
Dig Liver Dis. 2013 Oct;45(10):795-802. doi: 10.1016/j.dld.2013.02.002. Epub 2013 Mar 13.
Virtually any cell type in a mammalian organism uses Acetyl CoA to yield mevalonate, through the activity of the 3-hydroxy-3-methyl-glutaryl-CoA reductase enzyme and, ultimately, cholesterol. Statins have long and quite successfully been used as cholesterol lowering drugs. They reversibly inhibit the 3-hydroxy-3-methyl-glutaryl-CoA reductase activity, which is rate limiting in the early steps of the cholesterol synthesis pathway. In addition to these effects, it has also been amply shown that statins may efficiently trigger cancer cell apoptosis, making them a plausible therapeutic option for the treatment of cancer. Whether statins may prevent cancer occurrence is a matter of debate and an unanswered question; undoubtedly experimental models have clearly demonstrated the potential of statins as direct cytotoxic agents, which can reduce tumour development or metastasis spread, even more so when combined with cytotoxic drugs. Until now, however, only few data in humans support the idea that statins could rightfully belong to the group of anticancer drugs. Nevertheless, as cancer cell metabolism is being thoroughly revisited, the mevalonate pathway has recently been reported as truly oncogenic, presenting the attractive possibility that mevalonate pathway inhibitors, such as statins, may join the ranks of anticancer drugs.
实际上，哺乳动物体内的几乎任何细胞类型都可以通过 3-羟基-3-甲基戊二酰辅酶 A 还原酶的活性，将乙酰辅酶 A 转化为甲羟戊酸，最终生成胆固醇。他汀类药物长期以来一直被成功地用作降低胆固醇的药物。它们可逆地抑制 3-羟基-3-甲基戊二酰辅酶 A 还原酶的活性，而该酶在胆固醇合成途径的早期步骤中是限速酶。除了这些作用外，也充分表明他汀类药物可以有效地诱导癌细胞凋亡，使其成为治疗癌症的合理治疗选择。他汀类药物是否可以预防癌症的发生是一个有争议的问题，也是一个尚未解决的问题；毫无疑问，实验模型已经清楚地表明了他汀类药物作为直接细胞毒性剂的潜力，它们可以减少肿瘤的发展或转移扩散，当与细胞毒性药物联合使用时效果更为显著。然而，到目前为止，只有少数人类数据支持他汀类药物可以合理地属于抗癌药物这一观点。尽管如此，随着对癌细胞代谢的彻底重新研究，甲羟戊酸途径最近被报道为真正的致癌途径，这使得甲羟戊酸途径抑制剂（如他汀类药物）可能成为抗癌药物的一员，这一可能性具有吸引力。
