Cunha Júnior Ademar Dantas, Bragagnoli Arinilda Campos, Costa Felipe Osório, Carvalheira José Barreto Campello
Department of Internal Medicine, Division of Oncology, University of Campinas (UNICAMP), Campinas 13083-970, São Paulo, Brazil.
Division of Oncology, Hospital de Câncer de Barretos, Barretos 14784-400, São Paulo, Brazil.
World J Gastroenterol. 2021 May 7;27(17):1883-1904. doi: 10.3748/wjg.v27.i17.1883.
Diabetes mellitus type 2 and cancer share many risk factors. The pleiotropic insulin-dependent and insulin-independent effects of metformin might inhibit pathways that are frequently amplified in neoplastic tissue. Particularly, modulation of inflammation, metabolism, and cell cycle arrest are potential therapeutic cancer targets utilized by metformin to boost the anti-cancer effects of chemotherapy. Studies and models have demonstrated the potential of metformin as a chemo- and radiosensitizer, besides its chemopreventive and direct therapeutic activity in digestive system (DS) tumors. Hence, these aspects have been considered in many cancer clinical trials. Case-control and cohort studies and associated meta-analyses have evaluated DS cancer risk and metformin usage, especially in colorectal cancer, pancreatic cancer, and hepatocellular carcinoma. Most clinical studies have demonstrated the protective role of metformin in the risk for DS cancers and survival rates. On the other hand, the ability of metformin to enhance the actions of chemotherapy for gastric and biliary cancers is yet to be investigated. This article reviews the current findings on the anti-cancer mechanisms of metformin and its apparatus from pre-clinical and ongoing studies in DS malignancies.
2型糖尿病和癌症有许多共同的风险因素。二甲双胍的多效胰岛素依赖性和非胰岛素依赖性作用可能会抑制肿瘤组织中经常被放大的信号通路。特别是，炎症调节、代谢调节和细胞周期阻滞是二甲双胍用于增强化疗抗癌效果的潜在治疗性癌症靶点。研究和模型已经证明，除了在消化系统（DS）肿瘤中的化学预防和直接治疗活性外，二甲双胍还具有作为化疗增敏剂和放疗增敏剂的潜力。因此，许多癌症临床试验都考虑了这些方面。病例对照研究、队列研究及相关的荟萃分析评估了DS癌症风险和二甲双胍的使用情况，尤其是在结直肠癌、胰腺癌和肝细胞癌方面。大多数临床研究都证明了二甲双胍在DS癌症风险和生存率方面的保护作用。另一方面，二甲双胍增强胃癌和胆管癌化疗效果的能力尚待研究。本文综述了二甲双胍抗癌机制的当前研究结果及其在DS恶性肿瘤临床前和正在进行的研究中的作用。
