Study on the mechanism of radiotherapy inhibiting angioendothelioma via VEGFA/CXCL12/CXCR4 axis

Objective Angioendothelioma is a vascular tumor whose progression depends on angiogenesis. As a principal mediator of vascular growth, vascular endothelial growth factor A (VEGFA) plays a crucial role, though its precise involvement in angioendothelioma pathogenesis and its relationship with radiation treatment requires further exploration. This research focuses on examining VEGFA's contribution to angioendothelioma development and clarifying how radiation therapy exerts its antitumor effects by modulating the VEGFA/CXCL12/CXCR4 signaling cascade. Methods Through bioinformatics and multi-omics analyses, the researchers identified key molecular targets. In cellular studies, a stable cell line with modified gene expression was constructed using lentivirus-mediated gene transfer technology, and functional assessments were conducted by inhibiting and enhancing VEGFA expression. Comprehensive cell behavior experiments were performed to investigate the impact of VEGFA in the vascular endothelial microenvironment on malignant cell characteristics. The study further elucidated the CXCL12/CXCR4 signaling pathway by administering CXCR4 regulators to VEGFA-deficient cells, combined with CCK-8 proliferation assays, ELISA measurements of extracellular CXCL12 concentrations, and immunofluorescence analysis of CXCL12 protein localization. Results Experimental studies have demonstrated that deletion of the VEGFA gene significantly inhibits tumor cell proliferation. Radiotherapy (8 Gy) reduces VEGFA expression levels and attenuates the invasive properties of tumor cells; conversely, overexpression of VEGFA partially counteracts these effects. Molecular analysis reveals that VEGFA promotes tumor progression by activating the CXCL12/CXCR4 signaling pathway. Conclusion Radiotherapy can reduce VEGFA levels in angioendothelioma cells, and this downregulation of VEGFA contributes to the inhibition of the CXCL12/CXCR4 pathway—which mediates anti-proliferative and anti-invasive effects. It has been previously believed that the antitumor effects of radiotherapy are multifaceted, with direct DNA damage being one of the core mechanisms. Our study aims to elucidate additional molecular mechanisms associated with specific signaling pathways. This research offers novel therapeutic possibilities and conceptual support for managing vascular endothelial tumors.