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-1βsignaling pathway by Euryale shell polyphenols

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、CD_(4)^(+)和CD_(8)^(+)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CD_(4)^(+)、CD_(8)^(+)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。

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,CD_(4)^(+)and CD_(8)^(+)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 CD_(4)^(+)and CD_(8)^(+)T cells(P<0.01,P<0.05),improved antitumor immunity in mice,and decreased NLRP3,Cleaved-caspase-1/Caspase-1,ACS and IL-1βprotein expression(P<0.01).Conclusion:Euryale shell polyphenols can inhibit the activation of NLRP3 inflammasome and the release of inflammatory factors through NLRP3/IL-1βsignaling pathway,increase the recruitment of immune cells,antagonize the immunosuppression of lung cancer,and thus inhibiting the effect of subcutaneous tumors in mice.