EFFECT OF METFORMIN ON PATHWAYS RELATED TO CELL PROLIFERATION IN AN ENDOMETRIAL CANCER CELL LINE.
Metformin; Endometrial Neoplasia; In Vitro studies; Systematic Review
“Endometrial cancer (EC) is a gynaecologic neoplasm with a high incidence, associated with significant rates of mortality and morbidity among women. Its etiology has not been fully elucidated, however, metabolic and hormonal alterations are recognized for being related to its development. The primary recommended treatments are invasive surgical procedures, which may result in infertility, highlighting therapeutic limitations in specific scenarios and the need for alternatives with a better efficacy and safety profile. In this regard, metformin has been considered a promising candidate as an adjuvant treatment and is being studied to address gaps in the molecular mechanisms that may clarify its potential antitumor activity. Therefore, to expand the understanding of metformin’s mechanisms of action, the objective of this study was to investigate its effects, particularly on pathways associated with cell proliferation, through in vitro experiments and a systematic literature review. In the experimental assays, Ishikawa cells were treated with metformin (0.5, 15, and 40 mM for 48 hours), and the protein expression of AMPK, HIF1α, NFκB, and p70S6K was assessed by Western blot. The results indicated modulation of p70S6K and HIF1α under treatment with high concentration of metformin (40 mM), with no changes at low and intermediate concentrations, while AMPK and NFκB showed no significant differences under any condition. The systematic literature review followed the PICOS approach and included experimental studies in preclinical animal and cellular models of ECr, with metformin as a single intervention. The results from the systematic review corroborate metformin’s antiproliferative and pro-apoptotic effects in EC, as well as its ability to modulate cell cycle and several genes and proteins. Taken together, these findings suggest that metformin has potential as an adjuvant treatment for EC, while highlighting the need for further studies to deepen the understanding of its antitumor activity and to align laboratory findings with therapeutic dosing.”