Metformin regulation of progesterone receptor isoform-B expression in human endometrial cancer cells is glucose-dependent.

Metformin regulation of progesterone receptor isoform-B expression in human endometrial cancer cells is glucose-dependent. Oncol Lett. 2020 Nov;20(5):249 Authors: Saguyod SJU, Alhallak I, Simmen RCM, Velarde MC Abstract Metformin (MET) constitutes the first-line treatment against type 2 diabetes. Growing evidence linking insulin resistance and cancer risk has expanded the therapeutic potential of MET to several cancer types. However, the oncostatic mechanisms of MET are not well understood. MET has been shown to promote the expression of progesterone receptor (PGR) and other antitumor biomarkers in patients with non-diabetic endometrial cancer (EC) and in Ishikawa EC cells cultured in normal glucose (5.5 mM) media. Therefore, the present study aimed to assess the effects of MET on EC cells under conditions simulating diabetes. Ishikawa cells treated with 10 nM 17β-estradiol (E2) and/or 100 µM MET and exposed to normal and high (17.5 mM) concentrations of glucose were evaluated for proliferative and PGR expression status. Under normal glucose conditions, MET attenuated E2-induced cell proliferation and cyclin D1 gene expression, and increased total PGR and PGR-B transcript levels. MET inhibited Ishikawa cell spheroid formation only in the absence of E2 treatment. In E2-treated cells under high glucose conditions, MET showed no effects on cell proliferation and spheroid formation, and increased total PGR but not PGR-B transcript leve...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research