Sośnicki Stanisław, Kapral Małgorzata, Węglarz Ludmiła
School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Poland, Department of Biochemistry, Sosnowiec, Poland.
Pharmacol Rep. 2016 Oct;68(5):918-25. doi: 10.1016/j.pharep.2016.04.021. Epub 2016 May 9.
Epidemiological studies have shown that metformin, a first line therapeutic agent for diabetes mellitus, reduced the risk of developing various malignancies. Several preclinical studies established some possible mechanisms of its anticancer effects. The primary effect of metformin action is a decrease in cell energy status, which activates AMP-activated kinase (AMPK), a cellular metabolic sensor. This event is followed by a decrease in serum concentrations of insulin and insulin growth factor I (IGF-I), the potent mitogens for cancer cells. In addition to the indirect mode of action, metformin may exhibit direct inhibitory effect on cancer cells by targeting mammalian target of rapamycin (mTOR) signaling and anabolic processes. This review gathers information on mechanisms of metformin antitumor activity, with special attention given to the impact of this antidiabetic drug on insulin/PI3K/mTOR and AMPK signaling. Furthermore, the factors required for this novel activity of metformin are discussed.
流行病学研究表明，二甲双胍作为糖尿病的一线治疗药物，可降低患多种恶性肿瘤的风险。多项临床前研究确定了其抗癌作用的一些可能机制。二甲双胍作用的主要效应是细胞能量状态降低，这会激活细胞代谢传感器——AMP激活蛋白激酶（AMPK）。此事件之后，血清中胰岛素和胰岛素生长因子I（IGF-I）的浓度会降低，而胰岛素和胰岛素生长因子I是癌细胞的强效促有丝分裂原。除了间接作用模式外，二甲双胍还可能通过靶向雷帕霉素哺乳动物靶点（mTOR）信号传导和合成代谢过程对癌细胞表现出直接抑制作用。本综述收集了关于二甲双胍抗肿瘤活性机制的信息，特别关注这种抗糖尿病药物对胰岛素/PI3K/mTOR和AMPK信号传导的影响。此外，还讨论了二甲双胍这种新活性所需的因素。
