芡壳多酚通过调节NLRP3/IL-1β信号通路拮抗肺癌的免疫抑制研究
Study on immunosuppression of antagonizing lung cancer based on regulating NLRP3/IL-1β signaling pathway by Euryale shell polyphenols
单鑫 1向东阳 2陈璟 1吕志阳1
作者信息
- 1. 南京中医药大学翰林学院药学院,泰州 225300
- 2. 南京中医药大学中西医结合学院,南京 210046
- 折叠
摘要
目的:探讨芡壳多酚通过炎症因子抑制肺癌的作用及其机制.方法:通过腋下注射LLC细胞建立小鼠皮下瘤模型,分别给予不同剂量的芡壳多酚(6、12 g/kg)和5-氟尿嘧啶(20 mg/kg).对肿瘤组织进行HE染色、TUNEL凋亡染色、蛋白质印迹和免疫组织化学分析,评估小鼠肿瘤的形态、炎症环境、CD4+和CD8+T细胞浸润以及NLRP3炎症体相关蛋白的表达水平.结果:芡壳多酚可以有效抑制肿瘤增殖并促进细胞凋亡(P＜0.01,P＜0.05),改善肿瘤组织中炎症环境,增加CD4+、CD8+T细胞浸润(P＜0.01,P＜0.05),提高小鼠抗肿瘤免疫力,下调NLRP3、Cleaved-caspase-1/Caspase-1、ACS和IL-1β 的蛋白表达(P＜0.01).结论:芡壳多酚可能通过NLRP3/IL-1β信号阻碍NLRP3炎性体的激活和炎症因子的释放,增加免疫细胞募集,拮抗肺癌的免疫抑制,从而抑制小鼠皮下肿瘤的作用.
Abstract
Objective:To investigate the inhibitory effect of Euryale shell polyphenols on lung cancer through inflammatory factors and its mechanism.Methods:LLC cells were injected under the armpit of mice to establish subcutaneous tumor model.Different doses of Euryale shell polyphenols(6,12 g/kg)and 5-Fluorouracil(20 mg/kg)were given respectively.HE staining,TUNEL apoptosis staining,Western Blot and immunohistochemical analysis were performed to evaluate tumor morphology,inflammatory environment,CD4 and CD8+T cell infiltration,and NLRP3 inflammasome related protein expression.Results:Euryale shell polyphenols inhibited tumor proliferation and promoted cell apoptosis(P＜0.01,P＜0.05),improved the inflammatory environment in tumor tissues,and increased the infiltration of CD4+and CD8+T cells(P＜0.01,P＜0.05),improved anti-tumor immunity in mice,and decreased NLRP3,Cleaved-caspase-l/Caspase-1,ACS and IL-1 β protein expression(P＜0.01).Conclusion:Euryale shell polyphenols can inhibit the activation of NLRP3 inflammasome and the release of inflammatory factors through NLRP3/IL-1 β signaling pathway,increase the recruitment of immune cells,antagonize the immunosuppression of lung cancer,and thus inhibiting the effect of subcutaneous tumors in mice.
关键词
芡壳多酚/免疫抑制/NLRP3/IL-1β信号通路/LLC细胞/炎症微环境Key words
Euryale shell polyphenols/Immunosuppression/NLRP3/IL-1β signaling pathway/LLC cells/Inflammatory microenvironment引用本文复制引用
基金项目
泰州市科技支撑计划(农业)项目(TN202123)
江苏省高校自然科学基金项目(21KJB360018)
江苏省高校自然科学基金项目(22KJB360014)
江苏省中医药管理局项目(YB2020108)
出版年
2024
国家科技期刊平台
NSTL
万方数据