PMID- 28763435 OWN - NLM STAT- MEDLINE DCOM- 20180423 LR - 20210504 IS - 1643-3750 (Electronic) IS - 1234-1010 (Print) IS - 1234-1010 (Linking) VI - 23 DP - 2017 Aug 1 TI - Therapeutic Effect of Sodium Glucose Co-Transporter 2 Inhibitor Dapagliflozin on Renal Cell Carcinoma. PG - 3737-3745 AB - 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. FAU - Kuang, Haoyu AU - Kuang H AD - Department of Laboratory, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, China (mainland). FAU - Liao, Liya AU - Liao L AD - Department of Laboratory, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, China (mainland). FAU - Chen, Hongtao AU - Chen H AD - Department of Laboratory, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, China (mainland). FAU - Kang, Qian AU - Kang Q AD - Department of Laboratory, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, China (mainland). FAU - Shu, Xiaochun AU - Shu X AD - Department of Laboratory, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, China (mainland). FAU - Wang, Yanan AU - Wang Y AD - Department of Laboratory, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, China (mainland). LA - eng PT - Journal Article DEP - 20170801 PL - United States TA - Med Sci Monit JT - Medical science monitor : international medical journal of experimental and clinical research JID - 9609063 RN - 0 (Benzhydryl Compounds) RN - 0 (Glucosides) RN - 0 (RNA, Messenger) RN - 0 (Sodium-Glucose Transporter 2) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 1ULL0QJ8UC (dapagliflozin) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Benzhydryl Compounds/pharmacology/*therapeutic use MH - Carcinoma, Renal Cell/*drug therapy/pathology MH - Cell Cycle/drug effects MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Gene Expression Regulation, Neoplastic/drug effects MH - Glucose/metabolism MH - Glucosides/pharmacology/*therapeutic use MH - Humans MH - Kidney/drug effects/metabolism/pathology MH - Kidney Neoplasms/*drug therapy/pathology MH - Mice, Nude MH - RNA, Messenger/genetics/metabolism MH - Sodium-Glucose Transporter 2/genetics/metabolism MH - *Sodium-Glucose Transporter 2 Inhibitors PMC - PMC5549715 COIS- Conflict of interests The authors have declared that no competing interests exist. EDAT- 2017/08/02 06:00 MHDA- 2018/04/24 06:00 PMCR- 2017/08/01 CRDT- 2017/08/02 06:00 PHST- 2017/08/02 06:00 [entrez] PHST- 2017/08/02 06:00 [pubmed] PHST- 2018/04/24 06:00 [medline] PHST- 2017/08/01 00:00 [pmc-release] AID - 902530 [pii] AID - 10.12659/msm.902530 [doi] PST - epublish SO - Med Sci Monit. 2017 Aug 1;23:3737-3745. doi: 10.12659/msm.902530.