Loubière Camille, Dirat Béatrice, Tanti Jean-François, Bost Frédéric
Inserm U1065, centre méditerranéen de médecine moléculaire, équipe « physiopathologie cellulaire et moléculaire de l'obésité et du diabète », 06204 Nice, France.
Ann Endocrinol (Paris). 2013 May;74(2):130-6. doi: 10.1016/j.ando.2013.02.002. Epub 2013 Apr 12.
Cancer and type II diabetes are two diseases that appear to be associated. In fact, diabetes increases the incidence of several cancers (colon, endometrium, rectum and breast). Retrospective epidemiological studies show that metformin, a drug commonly used in type II diabetes, has antitumor properties. Therefore, many experimental studies (in vivo and in vitro) have been initiated in recent years to understand the cellular and molecular mechanisms that may explain the protective effects of metformin against cancer. Two main mode of action have been proposed. The first, indirect, involves the decrease of insulinemia. The second, via a direct action on cells, results in the regulation of the activated AMPK kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, which plays a central role in many cellular processes such as energy metabolism, protein synthesis, autophagy and apoptosis. Here, we review recent results concerning the antitumor action of metformin: epidemiological, metabolic, cellular and molecular levels. Ongoing experimental and clinical trials should help us better understand the mechanisms of action of metformin and allow us to determine whether the drug can be used in the treatment of cancer.
癌症与II型糖尿病是两种似乎存在关联的疾病。事实上，糖尿病会增加几种癌症（结肠癌、子宫内膜癌、直肠癌和乳腺癌）的发病率。回顾性流行病学研究表明，二甲双胍这种II型糖尿病常用药物具有抗肿瘤特性。因此，近年来开展了许多实验研究（体内和体外实验），以了解可能解释二甲双胍抗癌保护作用的细胞和分子机制。已提出两种主要作用模式。第一种是间接作用，涉及降低胰岛素血症。第二种是通过对细胞的直接作用，导致对活化的AMPK激酶（AMPK）/雷帕霉素哺乳动物靶蛋白（mTOR）通路的调节，该通路在许多细胞过程如能量代谢、蛋白质合成、自噬和凋亡中起核心作用。在此，我们综述了有关二甲双胍抗肿瘤作用的近期结果：包括流行病学、代谢、细胞和分子水平。正在进行的实验和临床试验应有助于我们更好地理解二甲双胍的作用机制，并使我们能够确定该药物是否可用于癌症治疗。
