He Wei, Yang Tong, Gong Xin-Hua, Qin Ru-Zhai, Zhang Xiao-Dong, Liu Wen-Dan
Department of Medical Oncology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 511447, P.R. China.
Department of Pathology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 511447, P.R. China.
Oncol Lett. 2018 Sep;16(3):3976-3982. doi: 10.3892/ol.2018.9076. Epub 2018 Jul 4.
An increasing volume of data indicates that disrupting the interaction between CXC motif chemokine receptor 4 (CXCR4) and its specific ligand, CXC motif chemokine 12 (CXCL12), may reduce tumor growth and metastasis. However, the translation from bench to bedside must be performed with extreme caution, as the CXCR4/CXCL12 axis is crucial for the normal development and maintenance of tissues and organs. In the present study, Cell Counting Kit-8 and Transwell migration assays were used to detect proliferation and chemotaxis of CXCR4-expressing A549 cells, a cell strain originating from human non-small-cell lung cancer (NSCLC), with or without the presence of AMD3100, a small-molecule inhibitor specific to CXCR4 signaling. In a xenograft model established by injecting nude mice with A549 cells, tumor growth, CXCR4 expression and microvessel density (MVD) in the tumor mass were determined through tumor size measurements and immunohistochemical staining following intraperitoneal administration of AMD3100 or vehicle. The results demonstrated that CXCR4 blockade inhibited the proliferation of A549 cells and their migration towards CXCL12 . Tumor growth, CXCR4 expression and MVD were markedly reduced in nude mice treated with AMD3100 compared with mice treated with the vehicle. In conclusion, the present data demonstrated that CXCR4 targeting impaired NSCLC cell growth, angiogenesis and metastatic spread, indicating that it may represent a novel treatment strategy for NSCLC.
越来越多的数据表明，破坏CXC基序趋化因子受体4（CXCR4）与其特异性配体CXC基序趋化因子12（CXCL12）之间的相互作用可能会减少肿瘤的生长和转移。然而，从实验室到临床的转化必须极其谨慎，因为CXCR4/CXCL12轴对于组织和器官的正常发育和维持至关重要。在本研究中，使用细胞计数试剂盒-8和Transwell迁移试验来检测表达CXCR4的A549细胞（一种源自人非小细胞肺癌（NSCLC）的细胞系）在有无CXCR4信号特异性小分子抑制剂AMD3100存在下的增殖和趋化性。在通过向裸鼠注射A549细胞建立的异种移植模型中，通过在腹腔注射AMD3100或赋形剂后测量肿瘤大小和进行免疫组织化学染色来确定肿瘤生长、肿瘤块中CXCR4的表达和微血管密度（MVD）。结果表明，CXCR4阻断抑制了A549细胞的增殖及其向CXCL12的迁移。与用赋形剂处理的小鼠相比，用AMD3100处理的裸鼠的肿瘤生长、CXCR4表达和MVD明显降低。总之，本研究数据表明，靶向CXCR4会损害NSCLC细胞的生长、血管生成和转移扩散，表明它可能代表一种NSCLC的新治疗策略。
