Division of Signalling Biology, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada M5G 2M9.
J Mol Endocrinol. 2012 Mar 29;48(3):R31-43. doi: 10.1530/JME-12-0007. Print 2012 Jun.
The anti-diabetic drug metformin is rapidly emerging as a potential anti-cancer agent. Metformin, effective in treating type 2 diabetes and the insulin resistance syndromes, improves insulin resistance by reducing hepatic gluconeogenesis and by enhancing glucose uptake by skeletal muscle. Epidemiological studies have consistently associated metformin use with decreased cancer incidence and cancer-related mortality. Furthermore, numerous preclinical and clinical studies have demonstrated anti-cancer effects of metformin, leading to an explosion of interest in evaluating this agent in human cancer. The effects of metformin on circulating insulin levels indicate a potential efficacy towards cancers associated with hyperinsulinaemia; however, metformin may also directly inhibit tumour growth. In this review, we describe the mechanism of action of metformin and summarise the epidemiological, clinical and preclinical evidence supporting a role for metformin in the treatment of cancer. In addition, the challenges associated with translating preclinical results into therapeutic benefit in the clinical setting will be discussed.
二甲双胍作为一种有潜力的抗癌药物，正在迅速崛起。二甲双胍有效治疗 2 型糖尿病和胰岛素抵抗综合征，通过减少肝糖异生和增强骨骼肌葡萄糖摄取来改善胰岛素抵抗。流行病学研究一致表明，二甲双胍的使用与癌症发病率和癌症相关死亡率的降低有关。此外，大量的临床前和临床研究已经证明了二甲双胍的抗癌作用，这导致人们对评估这种药物在人类癌症中的疗效产生了浓厚的兴趣。二甲双胍对循环胰岛素水平的影响表明其对与高胰岛素血症相关的癌症具有潜在疗效；然而，二甲双胍也可能直接抑制肿瘤生长。在这篇综述中，我们描述了二甲双胍的作用机制，并总结了支持二甲双胍在癌症治疗中发挥作用的流行病学、临床和临床前证据。此外，还将讨论将临床前结果转化为临床治疗益处所面临的挑战。
