Vacheron Albert, Wynn Anne, Zuber Jeff, Solomon Solomon S
Department of Medicine and Preventative Medicine, Research and Medical Service VAMC Memphis and Division of Endocrinology, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
Clin Res Diabetes Endocrinol. 2018;1(1).
The biguanide drug metformin used for treating Type 2 diabetes has anticancer properties and affects many pathways involving glucose metabolism, energy balance, and cell survival. A number of retrospective clinical studies have indicated a reduced risk of cancer and improved cancer outcomes in Type 2 diabetic patients taking metformin. Several of its effects are mediated through the induction of cellular stress and subsequent activation of AMP kinase, but many other mechanisms act independently of AMP kinase activation. Metformin has been shown to inhibit the effects of tumor necrosis factor (TNF)-alpha. TNF-alpha interferes with insulin signaling to produce insulin resistance in the insulin signaling pathway and promotes apoptosis through NF-KB in the apoptosis pathway. In addition, metformin reduces cellular proliferation by decreasing the amount of available insulin or by directly affecting the mammalian target of rapamycin complex involved with regulating protein synthesis. It can prevent tumors from acquiring stem cell-like properties, upregulate apoptotic pathways, and bolster the immune system's fight against cancer. Gaining a greater understanding of metformin's various mechanisms of action will continue to elucidate metformin's role as an effective treatment for cancer.
用于治疗2型糖尿病的双胍类药物二甲双胍具有抗癌特性，可影响许多涉及葡萄糖代谢、能量平衡和细胞存活的途径。多项回顾性临床研究表明，服用二甲双胍的2型糖尿病患者患癌风险降低，癌症预后改善。其一些作用是通过诱导细胞应激和随后激活AMP激酶介导的，但许多其他机制独立于AMP激酶激活发挥作用。已证明二甲双胍可抑制肿瘤坏死因子（TNF）-α的作用。TNF-α干扰胰岛素信号传导，在胰岛素信号通路中产生胰岛素抵抗，并通过凋亡途径中的NF-κB促进细胞凋亡。此外，二甲双胍通过减少可用胰岛素的量或直接影响参与调节蛋白质合成的雷帕霉素复合物的哺乳动物靶点来降低细胞增殖。它可以防止肿瘤获得干细胞样特性，上调凋亡途径，并增强免疫系统对抗癌症的能力。更深入地了解二甲双胍的各种作用机制将继续阐明其作为癌症有效治疗方法的作用。
