Gauthaman Kalamegam, Fong Chui-Yee, Bongso Ariff
Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074, Singapore.
J Cell Biochem. 2009 Apr 15;106(6):975-83. doi: 10.1002/jcb.22092.
The statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) were proven to be effective antilipid agents against cardiovascular disease. Recent reports demonstrate an anticancer effect induced by the statins through inhibition of cell proliferation, induction of apoptosis, or inhibition of angiogenesis. These effects are due to suppression of the mevalonate pathway leading to depletion of various downstream products that play an essential role in cell cycle progression, cell signaling, and membrane integrity. Recent evidence suggests a shared genomic fingerprint between embryonic stem cells, cancer cells, and cancer stem cells. Activation targets of NANOG, OCT4, SOX2, and c-MYC are more frequently overexpressed in certain tumors. In the absence of bona fide cancer stem cell lines, human embryonic stem cells, which have similar properties to cancer and cancer stem cells, have been an excellent model throwing light on the anticancer affects of various putative anticancer agents. It was shown that key cellular functions in karyotypically abnormal colorectal and ovarian cancer cells and human embryonic stem cells are inhibited by the statins and this is mediated via a suppression of this stemness pathway. The strategy for treatment of cancers may thus be the targeting of a putative cancer stem cell within the tumor with specific agents such as the statins with or without chemotherapy. The statins may thus play a dual prophylactic role as a lipid-lowering drug for the prevention of heart disease and as an anticancer agent to prevent certain cancers. This review examines the relationship between the statins, stem cells, and certain cancers.
他汀类药物（3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂）已被证明是有效的抗心血管疾病的降脂药物。最近的报告表明，他汀类药物可通过抑制细胞增殖、诱导细胞凋亡或抑制血管生成产生抗癌作用。这些作用是由于甲羟戊酸途径的抑制导致各种下游产物的消耗，这些下游产物在细胞周期进程、细胞信号传导和膜完整性中起重要作用。最近的证据表明，胚胎干细胞、癌细胞和癌症干细胞之间存在共同的基因组指纹。NANOG、OCT4、SOX2和c-MYC的激活靶点在某些肿瘤中更频繁地过度表达。在缺乏真正的癌症干细胞系的情况下，具有与癌症和癌症干细胞相似特性的人类胚胎干细胞，已成为一个很好的模型，有助于阐明各种假定的抗癌药物的抗癌作用。研究表明，他汀类药物可抑制核型异常的结直肠癌和卵巢癌细胞以及人类胚胎干细胞中的关键细胞功能，这是通过抑制这种干性途径介导的。因此，癌症治疗策略可能是用他汀类药物等特定药物靶向肿瘤内假定的癌症干细胞，可联合或不联合化疗。因此，他汀类药物可能具有双重预防作用，既作为预防心脏病的降脂药物，又作为预防某些癌症的抗癌药物。本综述探讨了他汀类药物、干细胞和某些癌症之间的关系。
