In silico prediction and in vitro and in vivo validation of acaricide fluazuron as a potential inhibitor of FGFR 3 and a candidate anticancer drug for bladder carcinoma

• Published in: Chemical biology & drug design Vol. 89; no. 4; pp. 505 - 513
• Main Authors: Ke, Kunbin, Li, Hongjian, Yao, Hong, Shi, Xi‐Nan, Dong, Chao, Zhu, Ying, Liu, Xu, Li, Ling, Leung, Kwong‐Sak, Wong, Man‐Hon, Liu, Xiao‐Dong, Kung, Hsiang‐fu, Lin, Marie Chia‐mi
• Format: Journal Article
• Language: English
• Published: 01.04.2017
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/cbdd.12872

Bladder carcinoma ( BC ) is the ninth most common cause of cancer worldwide. Surgical resection and conventional chemotherapy and radiotherapy will ultimately fail due to tumor recurrence and resistance. Thus, the development of novel treatment is urgently needed. Fibroblast growth factor receptor 3 ( FGFR 3) is an important and well‐established target for BC treatment. In this study, we utilized the free and open‐source protein–ligand docking software idock to prospectively identify potential inhibitors of FGFR 3 from 3,167 worldwide approved small‐molecule drugs using a repositioning strategy. Six high‐scoring compounds were purchased and tested in vitro. Among them, the acaricide drug fluazuron exhibited the highest antiproliferative effect in human BC cell lines RT 112 and RT 4. We further demonstrated that fluazuron treatment significantly increased the percentage of apoptosis cells, and decreased the phosphorylation level of FGFR 3 and its downstream proteins FRS 2‐α, AKT , and ERK . We also investigated the anticancer effect of fluazuron in vivo in BALB /C nude mice subcutaneously xenografted with RT 112 cells. Our results showed that oral treatment with fluazuron (80 mg/kg) significantly inhibited tumor growth. These results suggested for the first time that fluazuron is a potential inhibitor of FGFR 3 and a candidate anticancer drug for the treatment of BC .