Department of Urology, Beijing University of Chinese Medicine Shenzhen Hospital, Shenzhen, Guangdong 518172, P.R. China.
Department of Urology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
Oncol Rep. 2018 Sep;40(3):1666-1674. doi: 10.3892/or.2018.6546. Epub 2018 Jul 4.
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.
先前的研究发现，基质细胞衍生因子-1（SDF-1）/CXC 趋化因子受体-4（CXCR4）/β-连环蛋白信号的激活与癌症中的生物学恶性潜能有关。然而，其在膀胱癌（BCa）进展中的功能很少有报道。本研究旨在探讨 SDF-1/CXCR4 信号与β-连环蛋白在 BCa 细胞增殖、集落形成、迁移和侵袭中的关联。方法：采用 MTS、集落形成和 Transwell 迁移和侵袭实验，在 CXCR4 拮抗剂 AMD3465、SDF-1、β-连环蛋白拮抗剂 FH535、AMD3465+SDF-1 或 FH535+SDF-1 处理 SW780 细胞后进行。通过 RT-qPCR 和 Western blot 分别检测 mRNA 和蛋白水平。采用裸鼠模型评估 AMD3465 对 SW780 细胞异种移植瘤生长的影响。根据我们的结果，人膀胱癌 SW780 细胞被鉴定为具有高表达的 CXCR4 和β-连环蛋白。随后，我们发现 CXCR4 和β-连环蛋白拮抗剂均可显著抑制 SW780 细胞的增殖、集落形成、迁移和侵袭。值得注意的是，SDF-1 可逆转 AMD3465 和 FH535 对 SW780 细胞增殖、集落形成、迁移和侵袭的抑制作用。在 AMD3465 处理的 SW780 细胞中，SDF-1 存在时 c-myc 的表达明显上调，E-钙黏蛋白下调。此外，AMD3465 处理组的肿瘤体积和平均重量明显小于对照组，表明 AMD3465 可抑制 SW780 细胞在体内的生长。总之，靶向 SDF-1/CXCR4/β-连环蛋白轴可能是抑制 BCa 进展的潜在治疗靶点。
