Department of Hematology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China.
Department of Hematology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China.
Curr Probl Cancer. 2023 Aug;47(4):100972. doi: 10.1016/j.currproblcancer.2023.100972. Epub 2023 Jun 20.
Metformin is an ancient drug for the treatment of type 2 diabetes, and many studies now suggested that metformin can be used as an adjuvant drug in the treatment of many types of tumors. The mechanism of action of metformin for tumor treatment mainly involves: 1. activation of AMPK signaling pathway 2. inhibition of DNA damage repair in tumor cells 3. downregulation of IGF-1 expression 4. inhibition of chemoresistance and enhancement of chemotherapy sensitivity in tumor cells 5. enhancement of antitumor immunity 6. inhibition of oxidative phosphorylation (OXPHOS). Metformin also plays an important role in the treatment of hematologic tumors, especially in leukemia, lymphoma, and multiple myeloma (MM). The combination of metformin and chemotherapy enhances the efficacy of chemotherapy, and metformin reduces the progression of monoclonal gammopathy of undetermined significance (MGUS) to MM. The purpose of this review is to summarize the anticancer mechanism of metformin and the role and mechanism of action of metformin in hematologic tumors. We mainly summarize the studies related to metformin in hematologic tumors, including cellular experiments and animal experiments, as well as controlled clinical studies and clinical trials. In addition, we also focus on the possible side effects of metformin. Although a large number of preclinical and clinical studies have been performed and the role of metformin in preventing the progression of MGUS to MM has been demonstrated, metformin has not been approved for the treatment of hematologic tumors, which is related to the adverse effects of its high-dose application. Low-dose metformin reduces adverse effects and has been shown to alter the tumor microenvironment and enhance antitumor immune response, which is one of the main directions for future research.
二甲双胍是一种用于治疗 2 型糖尿病的古老药物，现在许多研究表明，二甲双胍可以作为多种肿瘤的辅助治疗药物。二甲双胍治疗肿瘤的作用机制主要包括：1. 激活 AMPK 信号通路；2. 抑制肿瘤细胞的 DNA 损伤修复；3. 下调 IGF-1 的表达；4. 抑制肿瘤细胞的化疗耐药性并增强化疗敏感性；5. 增强抗肿瘤免疫；6. 抑制氧化磷酸化（OXPHOS）。二甲双胍在血液系统肿瘤的治疗中也发挥着重要作用，特别是在白血病、淋巴瘤和多发性骨髓瘤（MM）中。二甲双胍与化疗的联合使用增强了化疗的疗效，并且二甲双胍降低了意义未明的单克隆丙种球蛋白血症（MGUS）向 MM 进展的风险。本文旨在总结二甲双胍的抗癌机制及其在血液系统肿瘤中的作用和作用机制。我们主要总结了二甲双胍在血液系统肿瘤中的相关研究，包括细胞实验和动物实验，以及对照临床试验和临床试验。此外，我们还重点关注了二甲双胍可能产生的副作用。尽管已经进行了大量的临床前和临床研究，并证明了二甲双胍在预防 MGUS 向 MM 进展方面的作用，但二甲双胍尚未被批准用于治疗血液系统肿瘤，这与其高剂量应用的不良反应有关。低剂量的二甲双胍可降低不良反应，并已被证明可改变肿瘤微环境并增强抗肿瘤免疫反应，这是未来研究的主要方向之一。
