Metformin: A promising drug for human cancers

Abstract

Small-molecule chemical drugs are of great significance for tumor-targeted and individualized therapies. However, the development of new small-molecule drugs, from basic experimental research and clinical trials to final application in clinical practice, is a long process that has a high cost. It takes at least 5 years for most drugs to be developed in the laboratory to prove their effectiveness and safety. Compared with the development of new drugs, repurposing traditional non-tumor drugs can be a shortcut. Metformin is a good model for a new use of an old drug. In recent years, the antitumor efficacy of metformin has attracted much attention. Epidemiological data and in vivo, and in vitro experiments have shown that metformin can reduce the incidence of cancer in patients with diabetes and has a strong antagonistic effect on metabolism-related tumors. Recent studies have shown that metformin can induce autophagy in esophageal cancer cells, mainly by inhibiting inflammatory signaling pathways. In recent years, studies have shown that the antitumor functions and mechanisms of metformin are multifaceted. The present study aims to review the application of metformin in tumor prevention and treatment.

Keywords: esophageal cancer; metformin; repurpose; treatment; tumor prevention.

Figure 1.

Chemical structure of metformin.

Figure 2.

Multiple functions of metformin. In addition to hypoglycemia, metformin displays antitumor, anti-aging, anti-Parkinson's disease and weight loss effects.

Figure 3.

Anti-neoplastic activity of metformin via inhibition of AMPK/mTOR pathway. Inhibition of AMPK/mTOR pathway leading to the arrest of protein synthesis is a major anti- neoplastic activity of metformin.

Figure 4.

Metformin induces esophageal cancer cell autophagy via the STAT3/Bcl-2/ATG pathway. Metformin inhibits STAT3 expression to decrease Bcl-2 protein expression, which upregulates expression of autophagy marker ATG, thus inducing autophagy to slow tumor growth of esophageal cancer.