The multifaceted effects of metformin on tumor microenvironment

Semin Cell Dev Biol. 2020 Feb;98:90-97. doi: 10.1016/j.semcdb.2019.05.010. Epub 2019 May 22.


The efficacy of metformin in treating cancer has been extensively investigated since epidemiologic studies associated this anti-diabetic drug with a lower risk of cancer incidence. Since tumors are complex systems, in which cancer cells coexist and interact with several different types of non-malignant cells, it is not surprising that anti-cancer drugs affect not only cancer cells, but also the abundance and functions of cells of the tumor microenvironment. Recent years have seen a wide collection of reports showing how metformin, as well as other complex I inhibitors, may influence cancer progression by modulating the phenotype of non-transformed cells in a tumor. In this review, we particularly focus on the effect of metformin on angiogenesis, cancer-associated fibroblasts, tumor-associated macrophages and cancer immunosuppression.

Keywords: Angiogenesis; Cancer immunosuppression; Cancer metabolism; Cancer-associated fibroblasts; Metformin; Respiratory complex I; Tumor microenvironment; Tumor-associated macrophages.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Fibroblasts / drug effects
  • Fibroblasts / pathology
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Macrophages / drug effects
  • Macrophages / pathology
  • Metformin / pharmacology*
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / pathology
  • Tumor Microenvironment / drug effects*


  • Antineoplastic Agents
  • Hypoglycemic Agents
  • Metformin