Cell line-specific modulation of colorectal cancer cell behavior following SGLT2 inhibition via empagliflozin

Abstract

Abstract Colorectal cancer (CRC) is a major global health problem, with type 2 diabetes mellitus (T2DM) and obesity among its significant risk factors. Empagliflozin (EMPA), a selective sodium–glucose cotransporter 2 (SGLT2) inhibitor widely used in the treatment of T2DM, has also demonstrated potential anticancer effects. However, reports of possible adverse effects in certain oncological contexts have raised concerns. We established several in vitro assays to evaluate the effects of EMPA on different colon cancer–derived cell lines. We applied proliferation, wound-healing, colony-formation, and CCK-8 assays, together with measurements of EMPA and glucose consumption, in HCT116, HT29, DLD1, SW480, and LS180 CRC cell lines. SGLT2 expression was confirmed in all cell lines. EMPA reduced proliferation in HT29 cells. Clonogenicity was decreased in HT29 and HCT116, but increased in DLD1 and SW480. Migration was reduced in DLD1, whereas enhanced migratory potential was observed in HT29 and HCT116. Cell viability was not significantly affected at the tested concentrations. HT29 cells showed significantly higher EMPA consumption compared with other lines. Glucose consumption differed among cell lines but was not altered by EMPA treatment. LS180 cells showed no significant response in the assessed parameters. EMPA was associated with ambivalent, cell line-specific effects on CRC cell behavior. While antitumor activity was observed in some models, enhanced migration and clonogenicity were detected in others. These findings warrant further investigation regarding the use of EMPA in patients with T2DM and concomitant CRC.