Abstract
BackgroundThe netrin-1 receptor UNC5B plays vital roles in angiogenesis, inflammation, embryonic development and carcinogenesis. However, the functional significance of UNC5B overexpression in bladder cancer remains unclear. In this study, we investigated the role of UNC5B in bladder cancer in vitro and in vivo.MethodsStable transfection of the human bladder cancer cell line 5637 with UNC5B (5637-U) was confirmed by real-time RT-PCR, western blot and immunofluorescence assays. UNC5B expression in 5637 and 5637-U cells and mice tumor specimens derived from these cell lines was analyzed by immunohistochemistryand western blotting. Changes in the levels of cell cycle proteins were evaluated by western blotting. Flow cytometry, CCK-8 and scratch tests were used to examine cell cycle distribution, proliferation and migration, respectively.ResultsUNC5B overexpression in 5637 cells inhibited cell multiplication and migration and induced cell cycle arrest at the G2/M phase, meanwhile exhibited changes in the expression of cell cycle-associated proteins, showing that UNC5B may inhibit metastatic behaviors in bladder cancer cells. In addition, tumors generated from 5637-U cells were smaller than tumors generated from control 5637 cells.ConclusionsOur findings suggest that UNC5B is a potential anti-neoplastic target in bladder cancer progression.
Highlights
The netrin-1 receptor UNC5B plays vital roles in angiogenesis, inflammation, embryonic development and carcinogenesis
The expression of UNC5B in 5637 with UNC5B (5637-U) cells and control 5637 cells was evaluated by real-time Realtimepolymerase chain reaction (RT-PCR) and western blot assays
Wound healing assays revealed significantly lower migration of 5637-U cells compared with 5637 cells (P < 0.05) (Fig. 2b)
Summary
The netrin-1 receptor UNC5B plays vital roles in angiogenesis, inflammation, embryonic development and carcinogenesis. The functional significance of UNC5B overexpression in bladder cancer remains unclear. We investigated the role of UNC5B in bladder cancer in vitro and in vivo. Despite recent improvements in bladder cancer therapies, mortality rates have remained constant [1]. The therapeutic potential of axon guidance factors and their corresponding receptors in cancer therapy has recently emerged. Kong et al BMC Cancer (2016) 16:892 evaluated the effect of UNC5B overexpression on cell proliferation and migration and the effect of UNC5B in tumors implanted in nude mice. We observed a significant decrease in proliferative and migratory activities after UNC5B transfection, and the size of masses under limbs was reduced in nude mice injected with UNC5Bexpressing cells
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