Metformin is associated with reduced cell proliferation in human endometrial cancer by inbibiting PI3K/AKT/mTOR signaling

Gynecol Endocrinol. 2018 May;34(5):428-432. doi: 10.1080/09513590.2017.1409714. Epub 2017 Nov 28.

Abstract

Metformin recently gained traction as potential anti-endometrial cancer agent for its new applications. However, the underlying mechanisms of the anti-cancer effect of metformin in the endometrial cancer have not yet been fully elucidated. Sixty-five patients diagnosed as endometrial carcinoma were grouped into (n = 33) and non-treatment mixed (n = 32) for analysis. Thirty healthy donors were recruited as controls. We attempt to investigate the effect of metformin on Ki-67, PI3K, p-AKT, p-S6K1, and p-4EBP1 staining in human endometrial cancer by immunohistochemical staining. We found that increased Ki-67 expression in women with endometrial cancer, which were reversed by conventional anti-diabetic doses of metformin in present work. In parallel, the reduced PI3K, p-AKT, p-S6K1, and p-4EBP1 staining induced by metformin appeared to play an important role for the anti-proliferative effects of metformin in endometrial cancer patients. Metformin significantly decreased proliferation in human endometrial cancer may by inhibiting PI3K/AKT/mTOR signaling. Our present results add to the growing body of evidence supporting metformin as a potential anti-cancer agent in endometrial cancer.

Keywords: Endometrial cancer; PI3K/AKT/mTOR; cell proliferation; metformin.

MeSH terms

  • Carcinoma / drug therapy*
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Cell Proliferation / drug effects*
  • Endometrial Neoplasms / drug therapy*
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / pathology
  • Endometrium / drug effects*
  • Endometrium / metabolism
  • Endometrium / pathology
  • Female
  • Humans
  • Metformin / pharmacology*
  • Metformin / therapeutic use
  • Middle Aged
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Metformin
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases