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01 August 2017 : Animal Research

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

Haoyu Kuang1ABEF, Liya Liao1BCD, Hongtao Chen1BC, Qian Kang1BE, Xiaochun Shu1E, Yanan Wang1G*

DOI: 10.12659/MSM.902530

Med Sci Monit 2017; 23:3737-3745

Abstract

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.

Keywords: Carcinoma, Renal Cell, Diabetes Mellitus, Type 2, Sodium-Glucose Transporter 2

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750