Long-Term Empagliflozin Treatment (50 Days) Attenuates Protease Activity, Migration, and Stemness-Associated...

Empagliflozin is a sodium-glucose cotransporter 2 inhibitor widely prescribed for the treatment of type 2 diabetes mellitus. It promotes urinary glucose excretion by inhibiting renal glucose reabsorption. Although empagliflozin has been widely used in clinical practice, its effects and underlying mechanisms related to metastasis, cytokine secretion, and stemness-associated phenotypes in renal pelvis transitional cell carcinoma (TCC) remain poorly understood. In this study, we investigated the long-term (50 days) effects of empagliflozin (5 μM) on BFTC-909 human renal pelvis TCC cells. Prolonged empagliflozin treatment suppressed the migration of tumor cells and the proteolytic activities of matrix metalloproteinase-2 and urokinase-type plasminogen activator. In addition, empagliflozin markedly reduced the viability and self-renewal capacity of BFTC-909 cells. Analysis of conditioned media revealed that long-term empagliflozin exposure significantly reduced the secretion of interleukin-1Ra, interleukin-8, granulocyte colony-stimulating factor, and vascular endothelial growth factor. Together, these findings suggest that empagliflozin suppresses the protease activity, tumor invasiveness, and stemness-associated phenotypes of renal pelvis TCC cells. Overall, this study indicates that long-term empagliflozin treatment reduces the metastatic potential of BFTC-909 renal pelvis TCC cells and highlights the need for additional in vivo and clinical investigations.