Kuang Haoyu, Liao Liya, Chen Hongtao, Kang Qian, Shu Xiaochun, Wang Yanan
Department of Laboratory, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, China (mainland).
Med Sci Monit. 2017 Aug 1;23:3737-3745. doi: 10.12659/msm.902530.
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.
2型糖尿病（T2DM）患者肾细胞癌（RCC）发病率高，且钠葡萄糖协同转运蛋白2（SGLT2）表达水平高。本研究旨在评估达格列净作为一种SGLT2抑制剂在体外和体内对RCC细胞系的抗癌活性。
采用qRT-PCR和蛋白质免疫印迹法检测不同人肾细胞上SGLT2的表达。然后，运用流式细胞术和免疫荧光法研究达格列净对CaKi-1细胞的细胞周期、凋亡及SGLT2表达的影响。最后，采用异种移植模型和免疫组织化学染色法研究达格列净在裸鼠体内的作用。
我们证实SGLT2在RCC细胞系中高表达。我们发现，达格列净对人RCC细胞的细胞毒性作用高于对正常人肾细胞的作用，可调节细胞周期和凋亡，并降低CaKi-1细胞的葡萄糖摄取及SGLT2表达。此外，达格列净在体内可抑制肿瘤生长并降低SGLT2表达。
我们的结果表明，达格列净具有高效低毒的特点，可能成为RCC的一种新的治疗靶点。
