Suppression of the SDF-1/CXCR4/-catenin axis contributes to bladder cancer cell growth inhibition in vitro and in vivo

摘要

Previous studies have found that the activation of stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor-4 (CXCR4)/-catenin signaling is associated with biological malignant potential in cancers. However, its function has been rarely reported in the progression of bladder cancer (BCa). The aim of the present study was to investigate the association of SDF-1/CXCR4 signaling and -catenin in regards to BCa cell proliferation, colony formation, migration and invasion. The methods used were MTS, colony formation, and Transwell migration and invasion assays which were performed in SW780 cells following treatment with the CXCR4 antagonist AMD3465, SDF-1, the -catenin antagonist FH535, AMD3465+SDF-1 or FH535+SDF-1. The mRNA and protein levels were assayed by RT-qPCR and western blotting, respectively. The effect of AMD3465 on SW780 cell xenograft growth in vivo was evaluated using a nude mouse model. According to our results, human BCa SW780 cells were identified as having high expression of CXCR4 and -catenin. Subsequently, we found that both CXCR4 and -catenin antagonists could significantly inhibit the proliferation, colony formation, migration and invasion of SW780 cells. Notably, SDF-1 could reverse the inhibitory effects of AMD3465 and FH535 on proliferation, colony formation, migration and invasion in SW780 cells. In AMD3465-treated SW780 cells, the expression of c-myc was significantly upregulated, and E-cadherin was downregulated in the presence of SDF-1. Furthermore, the tumor volume and average weight in the AMD3465-treated group were evidently less than these parameters in the control group, indicating that AMD3465 can inhibit SW780 cell growth in vivo. In conclusion, targeting the SDF-1/CXCR4/-catenin axis may be a potential therapeutic target for suppressing BCa progression.