Division of Endocrinology, Diabetes and Bone Diseases, Department of Medicine, Mount Sinai Medical Center, New York, New York 10029, USA.
Ann N Y Acad Sci. 2011 Dec;1243:54-68. doi: 10.1111/j.1749-6632.2011.06285.x.
Diabetes is associated with an increased risk of developing and dying from cancer. This increased risk may be due to hyperglycemia, hyperinsulinemia, and insulin resistance or other factors. Metformin has recently gained much attention as it appears to reduce cancer incidence and improve prognosis of patients with diabetes. In vitro data and animal studies support these findings from human epidemiological studies. Metformin has multiple potential mechanisms by which it inhibits cancer development and growth. For example, metaformin inhibits hepatic gluconeogenesis, thus decreasing circulating glucose levels, and it increases insulin sensitivity, thus reducing circulating insulin levels. Intracellularly, metformin activates AMPK, which decreases protein synthesis and cell proliferation. Metaformin also reduces aromatase activity in the stromal cells of the mammary gland. Finally, metformin may diminish the recurrence and aggressiveness of tumors by reducing the stem cell population and inhibiting epithelial to mesenchymal transition. Here, we discuss the metabolic abnormalities that occur in tumor development and some of the mechanisms through which metformin may alter these pathways and reduce tumor growth.
糖尿病与癌症的发生和死亡风险增加有关。这种风险增加可能是由于高血糖、高胰岛素血症和胰岛素抵抗或其他因素。二甲双胍最近受到了广泛关注，因为它似乎可以降低糖尿病患者的癌症发病率并改善其预后。体外数据和动物研究支持了这些来自人类流行病学研究的发现。二甲双胍具有多种抑制癌症发展和生长的潜在机制。例如，二甲双胍抑制肝糖异生，从而降低循环葡萄糖水平，增加胰岛素敏感性，从而降低循环胰岛素水平。在细胞内，二甲双胍激活 AMPK，减少蛋白质合成和细胞增殖。二甲双胍还通过降低乳腺基质细胞中的芳香酶活性来减少肿瘤的复发和侵袭性。最后，二甲双胍可能通过减少干细胞群并抑制上皮间质转化来减少肿瘤的复发和侵袭性。在这里，我们讨论了肿瘤发生过程中发生的代谢异常，以及二甲双胍可能改变这些途径并减少肿瘤生长的一些机制。
