Skuli Sarah J, Alomari Safwan, Gaitsch Hallie, Bakayoko A'ishah, Skuli Nicolas, Tyler Betty M
Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Hunterian Neurosurgical Research Laboratory, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Pharmaceuticals (Basel). 2022 May 19;15(5):626. doi: 10.3390/ph15050626.
The deregulation of energetic and cellular metabolism is a signature of cancer cells. Thus, drugs targeting cancer cell metabolism may have promising therapeutic potential. Previous reports demonstrate that the widely used normoglycemic agent, metformin, can decrease the risk of cancer in type 2 diabetics and inhibit cell growth in various cancers, including pancreatic, colon, prostate, ovarian, and breast cancer. While metformin is a known adenosine monophosphate-activated protein kinase (AMPK) agonist and an inhibitor of the electron transport chain complex I, its mechanism of action in cancer cells as well as its effect on cancer metabolism is not clearly established. In this review, we will give an update on the role of metformin as an antitumoral agent and detail relevant evidence on the potential use and mechanisms of action of metformin in cancer. Analyzing antitumoral, signaling, and metabolic impacts of metformin on cancer cells may provide promising new therapeutic strategies in oncology.
能量代谢和细胞代谢的失调是癌细胞的一个特征。因此,靶向癌细胞代谢的药物可能具有广阔的治疗潜力。先前的报道表明,广泛使用的血糖正常化药物二甲双胍可以降低2型糖尿病患者患癌风险,并抑制包括胰腺癌、结肠癌、前列腺癌、卵巢癌和乳腺癌在内的多种癌症的细胞生长。虽然二甲双胍是一种已知的单磷酸腺苷激活蛋白激酶(AMPK)激动剂和电子传递链复合体I的抑制剂,但其在癌细胞中的作用机制以及对癌症代谢的影响尚未明确。在这篇综述中,我们将更新二甲双胍作为抗肿瘤药物的作用,并详细阐述有关二甲双胍在癌症中的潜在用途和作用机制的相关证据。分析二甲双胍对癌细胞的抗肿瘤、信号传导和代谢影响可能会为肿瘤学提供有前景的新治疗策略。