Metformin and malignant neoplasms: a possible mechanism of antitumor action and prospects for use in practice

• Published in: Problemy ėndokrinologii 2022-07, Vol.68 (5), p.45-55
• Main Authors: Kuznetsov, K. O., Safina, E. R., Gaimakova, D. V., Frolova, Ya. S., Oganesyan, I. Yu, Sadertdinova, A. G., Nazmieva, K. A., Islamgulov, A. H., Karimova, A. R., Galimova, A. M., Rizvanova, E. V.
• Format: Article
• Language: English
• ISSN: 0375-9660; 2308-1430
• DOI: 10.14341/probl13097

Metformin is a first-line antidiabetic drug for the treatment of type 2 diabetes mellitus (DM2); its molecular target is AMP-activated protein kinase (AMPK), which is involved in many metabolic processes. Metformin not only reduces blood glucose levels and improves insulin sensitivity, but also inhibits lipolysis and reduces cardiovascular risk in patients with DM2. In recent years, it has been proven that metformin slows down the aging process, stimulates hair growth, eliminates cognitive impairment, and also has an antitumor effect. Most basic studies have shown that metformin inhibits the growth of tumor cells and promotes cellular apoptosis, while clinical studies show contradictory results. This discrepancy can be explained by the difference in the concentration of metformin between basic and clinical studies. The maximum daily dose of metformin for patients with DM2 is 2500 mg / day, and the dose used in basic research was much higher. Metformin directly activates the AMPK signaling pathway, inhibits the production of reactive oxygen species, induces the activation of mTORC1, inhibits cyclin D1, which leads to a reduction in the risk of the occurrence and development of malignant neoplasms. In addition, metformin indirectly inhibits tumor growth, proliferation, invasion and metastasis by reducing the concentration of glucose in the blood, insulin resistance, as well as by reducing inflammation and affecting the tumor microenvironment. Glycolysis plays an important role in the energy metabolism of tumors, and metformin is able to have an inhibitory effect on it. Currently, studies of the mechanism of antitumor effects of metformin are becoming more extensive and in-depth, but there are still some contradictions.