Therapeutic Effect of Sodium Glucose Co-Transporter 2 Inhibitor Dapagliflozin on Renal Cell Carcinoma

BACKGROUND Patients with type 2 diabetes mellitus (T2DM) have a high incidence of renal cell carcinoma (RCC) and high sodium glucose co-transporters 2 (SGLT2) expressions. The purpose of this study was to evaluate the anticancer activity of dapagliflozin as an SGLT2 inhibitor on RCC cell lines in vitro and in vivo. MATERIAL AND METHODS qRT-PCR and Western blot were used to detect SGLT2 expression on different human renal cells. Then, flow cytometry and immunofluorescence were used to investigate the effects of dapagliflozin on cell cycle, apoptosis, and SGLT2 expression of CaKi-1 cells. Finally, a xenograft model and immunohistochemical staining were used to investigate the function of dapagliflozin in nude mice. RESULTS We proved that SGLT2 is highly expressed in RCC cell lines. We found that dapagliflozin exerts a higher cytotoxic effect on human RCC than on normal human renal cells, regulates the cell cycle and apoptosis, and reduces the glucose uptake and SGLT2 expression of CaKi-1 cells. Moreover, dapagliflozin inhibits tumor growth and reduces SGLT2 expression in vivo. CONCLUSIONS Our results indicate that dapagliflozin has high efficiency and low toxicity and could be a new therapeutic target for RCC.