Metformin Affects Endometrial Carcinoma Cell Proliferation and Apoptosis by Regulating the Prognostic Marker S100a2 Expression
Indian Journal of Pharmaceutical Education and Research
Abstract
Background: To investigate the effects of metformin on the proliferation and apoptosis of human endometrial carcinoma cells, along with elucidating the potential underlying mechanisms, we conducted a study wherein the candidate prognostic gene associated with endometrial carcinoma progression was identified through bioinformatics analysis. Materials and Methods: Endometrial carcinoma cells Ishikawa were treated with metformin at concentrations of 5, 10 and 20 mmol/L. Cell proliferation and apoptosis were assessed using Cell Counting Kit-8 (CCK-8) assays, clone formation tests and flow cytometry analysis. Additionally, immunofluorescence staining was performed to detect the expression of the apoptotic marker Caspase-1. The mRNA levels of S100 calcium binding protein A2 (S100A2), Phosphatidylinositol-4,5-bisphosphate 3-Kinase (PI3K), serine/Threonine Kinase 1 (AKT), BCL2 associated x (Bax) and B-cell lymphoma 2 (Bcl-2) were quantified by Real-Time quantitative Reverse Transition PCR (qRT-PCR). Results: The results indicated that S100A2 is a potential prognostic gene influencing the pathogenesis of endometrial carcinoma. Metformin inhibited the proliferation and clone formation of Ishikawa cells in a dose-dependent manner, while also significantly increasing the apoptotic rate of these cells (p<0.05). Furthermore, metformin dose-dependently upregulated Caspase-1 protein expression and downregulated the mRNA levels of S100A2, PI3K, AKT and Bcl-2, as well as increasing the expression of Bax mRNA (p<0.05). Conclusion: We concluded that metformin inhibits cell proliferation and promotes apoptosis in endometrial carcinoma, potentially through the regulation of S100A2 expression. These findings may offer new insights into the development of therapeutic targets for endometrial carcinoma in the future.
Keywords
- Endometriosis (EMS)
- Human endometrial stromal cells (HESCs)
- Proliferation
- Invasion
- Wnt/β-catenin