Empagliflozin Inhibits OSCC Proliferation and Migration by Suppressing SLC2A3 and NLRP3

Aim: High glucose and inflammation facilitate oral squamous cell carcinoma (OSCC) progression. The glucose transporter solute carrier family 2 member 3 (SLC2A3) and the nucleotide-binding oligomerization domain, leucine-rich repeat-containing family pyrin domain containing 3 (NLRP3), contribute to chronic inflammation and poor prognosis. This study investigates the regulatory effects of the antidiabetic drug empagliflozin (emp) on SLC2A3 and NLRP3 in OSCC and their impact on cancer cell growth. Materials and Methods: Human OSCC cell lines, SCCL-MT1 and UPSI-SCC-131, were cultured in Dulbecco’s Modified Eagle Medium with supplements. Emp, lipopolysaccharide, and adenosine triphosphate were used for treatments. Real-time polymerase chain reaction quantified SLC2A3 and NLRP3 expressions. Enzyme-linked immunosorbent assay measured interleukin-1beta (IL-1β) levels, and cell proliferation was assessed using the xCELLigence system. Migration was evaluated via a scratch wound assay. Protein-protein interactions were predicted using the STRING database. Data analysis was conducted using GraphPad Prism. Results: Emp, an SGLT2 inhibitor, significantly reduced SLC2A3 (p<0.0001, p=0.0002; respectively) and NLRP3 expression (p=0.0008; p=0.0006; respectively), leading to decreased IL-1β release (p=0.0190, p<0.0001; respectively), proliferation (p=0.024; p<0.0001; respectively), and migration (p=0.0021; p=0.0004, respectively) in SCCL-MT1 and UPSI-SCC131 OSCC cell lines. These findings suggest emp’s potential as a therapeutic agent for OSCC by targeting glucose metabolism and inflammation. Conclusion: These findings suggest that emp effectively modulates glucose metabolism and inflammation in OSCC by inhibiting SLC2A3 and NLRP3 expression and IL-1β release, thereby reducing cancer cell proliferation and migration, highlighting its possible role as a treatment option for managing OSCC progression.