CXCL5 Promotes Gastric Cancer via Modulating NF-κB and Wnt/β-catenin Signaling-mediated Inhibition of Tumor Immune

Objective To investigate the role of CXCL5 in promoting gastric cancer and the potential molecular mechanisms.

Methods We selected 83 gastric cancer patients as study objects and 40 healthy people who underwent physical examination as control. We compared the serum levels of CXCL5 between gastric cancer patients and healthy control, and the expression of CXCL5 and CXCR2 between tumor and paracarcinoma tissues. The effect of CXCL5 on ERK/MAPK, PI3K/AKT, NF-κB and WNT/β-catenin signals were examined. CXCL5-overexpressed and control MFC cells were injected subcutaneously into C57 mice to establish xenograft model. Tumor growth and survival curves were drawn. The expression of CXCL5, p-NF-κB and p-β-catenin and the number of CD4⁺ T, CD8⁺ T and CD56⁺CD16⁺ NK cells in xenograft tumor tissue were determined.

Results CXCL5 expression in the serum of gastric cancer patients was significant higher than that in healthy controls (P < 0.05). The expression of CXCL5 and CXCR2 in tumor tissues were significantly higher than those in paracarcinoma normal tissues (P < 0.05). CXCL5 increased the expression of p-NF-κB and p-β-catenin in SNU126 and MFC cells (P < 0.05). In CXCL5 overexpression group, the tumor volume significantly increased and the survival of mice were significantly decreased, the expression levels of CXCL5, p-NF-κB and p-β-catenin were significantly higher, the number of CD4⁺T, CD8⁺T and CD56⁺CD16⁺ NK cells were significantly higher, compared with control mice (all P < 0.05).

Conclusion CXCL5 may promote gastric cancer via modulating NF-κB and Wnt/β-catenin signaling-mediated inhibition of tumor immune.