Pawałowska Monika, Markowska Anna
Department of Oncology, Poznan University of Medical Sciences, Poznan, Poland.
Contemp Oncol (Pozn). 2012;16(3):223-9. doi: 10.5114/wo.2012.29289. Epub 2012 Jul 6.
Obesity, hypertension and glucose tolerance disorders have become a growing concern in recent years. It is estimated that over 220 million people suffer from diabetes. It is a condition conducive to cardiovascular diseases, nephropathy, retinopathy and neuropathy but also to the development of many types of cancer. Insulin resistance and hyperinsulinemia lead to increased concentration of insulin-like growth factors, activation of IGF-R receptors, activation of PI3K and Ras-Raf pathways and result in increased cell division. The greatest risk is associated with developing stomach, pancreatic, colorectal, esophageal and lung cancer as well as breast and cervical cancer. Numerous cohort studies have confirmed that diabetic patients treated with metformin show a lower cancer morbidity and mortality rate. The dominant mechanism of action is activation of the AMP-activated protein kinase (AMPK) pathway and inhibition of mTOR protein, the key protein to regulate cell growth, apoptosis, proliferation and protein synthesis. Many clinical trials are currently under way to investigate the effectiveness of metformin in the prevention and treatment of neoplasms.
近年来，肥胖、高血压和糖耐量异常已成为日益受到关注的问题。据估计，超过2.2亿人患有糖尿病。糖尿病不仅会引发心血管疾病、肾病、视网膜病变和神经病变，还会促使多种癌症的发生。胰岛素抵抗和高胰岛素血症会导致胰岛素样生长因子浓度升高，IGF-R受体激活，PI3K和Ras-Raf信号通路激活，进而导致细胞分裂增加。患胃癌、胰腺癌、结直肠癌、食管癌和肺癌以及乳腺癌和宫颈癌的风险最高。大量队列研究证实，接受二甲双胍治疗的糖尿病患者癌症发病率和死亡率较低。其主要作用机制是激活AMP激活的蛋白激酶（AMPK）信号通路并抑制mTOR蛋白，mTOR蛋白是调节细胞生长、凋亡、增殖和蛋白质合成的关键蛋白。目前正在进行许多临床试验，以研究二甲双胍在预防和治疗肿瘤方面的有效性。
