HMGB1 induces proliferation of lung cancer cells and suppresses immune cell function via NF-κB pathway
10.3969/j.issn.1000-484X.2025.03.020
- VernacularTitle:HMGB1藉由NF-κB通路诱导肺癌细胞增殖并抑制免疫细胞功能
- Author:
Yaohui WANG
1
;
Yu MENG
;
Yike QIAN
;
Wenli CHEN
;
Rongyu LI
;
Bohan DONG
Author Information
1. 皖南医学院微生物学与免疫学教研室,芜湖 241000
- Publication Type:Journal Article
- Keywords:
Anti-tumor immunity;
Apoptosis;
NF-κB signaling pathway;
Macrophages;
Mouse spleen cells;
Lung cancer
- From:
Chinese Journal of Immunology
2025;41(3):628-633
- CountryChina
- Language:Chinese
-
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.
