Stromal cell-derived factor-1 (SDF-1) is a member of the cysteine-X-cysteine class of chemokines, and achieves its biological functions by binding to the CXC chemokine receptor 4 (CXCR4) and CXCR7 (5). SDF-1 and CXCR4

Previous studies have found that the activation of stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor-4 (CXCR4)/β-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 β-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 β-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 β-catenin. Subsequently, we found that both CXCR4 and β‐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/β-catenin axis may be a potential therapeutic target for suppressing BCa progression. Introduction Bladder cancer (BCa) is one of the most commonly diagnosed urologic malignant tumor and remains life-threatening due to its high occurrence of metastases. The 5-year BCa survival rate is <60% (1). Each year ~80,500 patients are diagnosed with BCa, and 32,900 cancer-related deaths were reported to a population-based cancer registry (2009-2011) in China (2). Cisplatin-based chemotherapy combined with radical cystectomy is the recommended treatment strategy in routine clinical practice (3,4); however, the outcome of BCa patients is usually ineffective or poorly tolerated. Therefore, it is imperative to explore new potential molecular mechanisms that may provide better therapeutic targets and achieve better therapeutic efficacy to decrease the mortality rate of patients with BCa. Stromal cell-derived factor-1 (SDF-1) is a member of the cysteine-X-cysteine class of chemokines, and achieves its biological functions by binding to the CXC chemokine receptor 4 (CXCR4) and CXCR7 (5). SDF-1 and CXCR4 are widely expressed in a variety of cells and tissues (6). The expression of CXCR4 in malignant epithelial cells and cells from several hematopoietic malignancies indicates that the SDF-1/CXCR4 pathway may influence the biology of cancer (7). Upregulation of SDF-1 and CXCR4 has been associated with poor prognosis in various human cancers, including ovarian (8), head and neck (9), rectal (10) and breast (11) cancers. A growing number of studies has demonstrated that the SDF-1/CXCR4 chemokine pathway promotes the survival, proliferation and migration of cancer cells (12-14), indicating that interruption to the SDF-1/CXCR4 axis may be a new therapeutic strategy to inhibit cancer metastasis. SDF-1 and CXCR4 are also involved in the progression of BCa (15,16). Gosalbez et al found that the expression of SDF-1 was increased in bladder tumors and was related with high-grade tumors and metastasis (16). CXCR4-positive BCa cell exposure to SDF‐1 provoked a significant increase in both cell migration and invasion abilities (17). Previous studies have demonstrated that SDF-1/CXCR4 may induce cancer cell proliferation, and invasion through activation of the Wnt/β-catenin signaling pathway (18-20). Specifically, the Wnt/β-catenin signaling pathway is a key modulator of cellular proliferation (21). In addition, β-catenin as a transcriptional co-regulator cooperates with transcription Suppression of the SDF‐1/CXCR4/β‐catenin axis contributes to bladder cancer cell growth inhibition in vitro and in vivo TAO ZHANG1, FEI YANG2, WENBIAO LI2, BOLONG LIU2, WENDE LI3, ZHIYI CHEN1 and CAN WANG1 1Department of Urology, Beijing University of Chinese Medicine Shenzhen Hospital, Shenzhen, Guangdong 518172; 2Department of Urology, The Third Affiliated Hospital of Sun Yat‐sen University, Guangzhou, Guangdong 510630; 3Guangdong Laboratory Animals Monitoring Institute, Guangzhou, Guangdong 510260, P.R. China Received December 29, 2017; Accepted June 27, 2018 DOI: 10.3892/or.2018. 6546 Correspondence to: Dr Tao Zhang, Department of Urology, Beijing University of Chinese Medicine Shenzhen Hospital, 1 Dayun Road, Longgang, Shenzhen, Guangdong 518172, P.R. China E-mail: zhangtaomed@163.com