趋化因子CXCL5调控NF-κB与Wnt/β-catenin信号通路抑制肿瘤免疫促进胃癌的机制研究

刘立; 盖金娜; 尹作文; 陈琴华

doi:10.3971/j.issn.1000-8578.2020.19.1156

趋化因子CXCL5调控NF-κB与Wnt/β-catenin信号通路抑制肿瘤免疫促进胃癌的机制研究

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

摘要

摘要:
目的探讨CXC趋化因子配体-5（CXCL5）促进胃癌的作用及其潜在分子机制。
方法纳入胃癌患者83例，另选取健康者40例作为对照。比较两者的血清CXCL5水平; 比较癌组织及癌旁正常组织中CXCL5与CXCR2的表达。检测CXCL5对胃癌细胞ERK/MAPK、PI3K/AKT、NF-κB及Wnt/β-catenin信号通路的影响。用对照与过表达CXCL5的MFC细胞建立胃癌移植瘤模型，记录肿瘤生长和小鼠生存曲线; 检测各组小鼠移植瘤中CXCL5、p-NF-κB与p-β-catenin的表达及CD4⁺T、CD8⁺T与CD56⁺CD16⁺NK细胞数量。
结果胃癌患者的血清CXCL5水平较健康者显著升高（P < 0.05）。癌组织中CXCL5与CXCR2的表达较癌旁正常组织显著升高（P < 0.05）。CXCL5能显著增加SNU216与MFC细胞p-NF-κB与p-β-catenin的表达（均P < 0.05）。与对照组小鼠相比，过表达CXCL5组小鼠的肿瘤体积显著增高（P < 0.05），生存期显著降低（P < 0.05），癌组织中CXCL5、p-NF-κB与p-β-catenin的表达显著升高（P < 0.05），癌组织中CD4⁺T、CD8⁺T与CD56⁺CD16⁺NK细胞数量均显著降低（均P < 0.05）。
结论 CXCL5可能通过调控NF-κB与Wnt/β-catenin信号通路抑制肿瘤免疫从而发挥促进胃癌的作用。

Abstract:
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.

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