摘要Numerous studies have demonstrated that the high expression of CXC motif chemokine ligand 16(CXCL16)in cancer correlates with poor prognosis,as well as tumor cell proliferation,migration,and invasion.While CXCL16 can serve as a tumor biomarker,the underlying mechanism in modulating head and neck squamous cell carcinoma(HNSCC)remains unclear.In this study,the aimed was to investigate the CXCL16 expression in HNSCC and to uncover the potential underlying mechanism.Hereby,we determined the high expression of CXCL16 in The Cancer Genome Atlas(TCGA)database,as well as in tissue samples from patients with HNSCC at our central hospital and from HNSCC cell lines.The results showed that CXCL16 knockdown inhibited the proliferation,migration,and invasion of HNSCC cells.Mechanistically,transcriptome sequencing revealed that CXCL16 may affect HNSCC cell growth by regulating the antioxidant pathway of glutathione peroxidase 1(GPX1).The reactive oxygen species(ROS)levels were elevated in small interfering CXCL16(si-CXCL16)cells,which may contribute to the inhibition of cell proliferation,migration,and invasion.Moreover,treatment of cells with the GPX1 inhibitor eldecalcitol(ED-71)revealed that HNSCC cell growth was significantly inhibited in the synergistic group of si-CXCL16 and GPX1 inhibitor compared to the si-CXCL16 group.In conclusion,CXCL16 contributed to the development of HNSCC cells by modulating the GPX1-mediated antioxidant pathway.Thus,targeting cellular CXCL16 expression seems to be a promising strategy for treating HNSCC.