中国免疫学杂志2025，Vol.41Issue(3)：628-633,6.DOI:10.3969/j.issn.1000-484X.2025.03.020
HMGB1藉由NF-κB通路诱导肺癌细胞增殖并抑制免疫细胞功能
HMGB1 induces proliferation of lung cancer cells and suppresses immune cell function via NF-κB pathway
摘要
Abstract
Objective:To investigate the molecular mechanisms by which HMGB1 in lung cancer cells affects the function of lung cancer cells themselves and immune cells through the NF-κB pathway.Methods:Western blot detected HMGB1 expressions in Lewis lung cancer(LLC)cells,Raw264.7 cells,and mouse spleen cells,while tumor cell lysates(TCL)with low HMGB1 was pre-pared by inhibiting HMGB1 expression in lung cancer cells with glycyrrhetinic acid(GA);the effects of endogenous HMGB1 inhibi-tion or TCL with low HMGB1 on apoptosis and proliferation of lung cancer cells were detected by flow cytometry and CCK-8;TCL with normal HMGB1 or TCL with low HMGB1 was prepared by freeze-thawing;Raw264.7 cells and mouse splenocytes were treated with them for 48 h.Apoptosis and CD69 expression were detected by flow cytometry,and secretion of cytokines IL-2,IL-4,IL-6,TNF-α and TNF-β were detected by ELISA;Western blot detected lung cancer cells or immune cells.Western blot was performed to detect the protein expression of key signaling molecules of the NF-κB signaling pathway in lung cancer cells or immune cells.Results:HMGB1 was expressed in LLC cells,Raw264.7 cells,and mouse spleen cells,among which LLC cells had the highest expression of HMGB1,and 30 µg/ml GA had the best inhibitory effect on HMGB1 expression in LLC cells.Endogenous HMGB1 in LLC cells could promote cell proliferation.Exogenous HMGB1 in TCL induced apoptosis in lung cancer cells and inhibited immune cell activation and prolifera-tion.Inhibition of endogenous HMGB1 in lung cancer cells leaded to activation of the apoptosis-inducing factor CASP9 in the NF-κB signaling pathway,which was inhibited in lung cancer cells or immune cells after the action of TCL with low HMGB1.Conclusion:Tumor cell HMGB1 has a dual role in lung carcinogenesis,promoting the proliferation of lung cancer cells while suppressing the func-tion of immune cells,which in turn causes lung carcinogenesis,a process associated with the activation of the NF-κB signaling path-way in different cells.关键词
抗肿瘤免疫/细胞凋亡/NF-κB信号通路/巨噬细胞/小鼠脾细胞/肺癌Key words
Anti-tumor immunity/Apoptosis/NF-κB signaling pathway/Macrophages/Mouse spleen cells/Lung cancer分类
医药卫生引用本文复制引用
王耀辉,孟宇,钱一可,陈文利,厉荣玉,董博翰..HMGB1藉由NF-κB通路诱导肺癌细胞增殖并抑制免疫细胞功能[J].中国免疫学杂志,2025,41(3):628-633,6.基金项目
国家自然科学基金青年基金项目(81402351) （81402351）
安徽省教育厅自然科学研究项目(KJ2019A0415) （KJ2019A0415）
安徽省高校优秀青年人才支持计划(重点)(gxyqZD2019040) （重点）
皖南医学院学术和技术带头人后备人选 （）
皖南医学院2020年青年卓越人才培养项目(wyqnyx202001). （wyqnyx202001）
