Targeting CXC motif chemokine receptor 4 inhibits the proliferation, migration and angiogenesis of lung cancer cells.

Abstract

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 in vitro 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 in vitro. 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.