摘要
目的:明确桦褐孔菌多糖(IOP)是否通过激活NF-κB和NLRP3通路阻止结肠炎相关结直肠癌(CAC)的发生发展。方法:IOP处理SW620细胞,CCK-8测定细胞活力;RT-PCR和Western blot法分别检测NLRP3/NF-κB信号通路中相关基因、蛋白及细胞凋亡相关基因、蛋白水平。以氧化偶氮甲烷/葡聚糖硫酸钠(AOM/DSS)诱导CAC小鼠模型,记录小鼠体重及结肠腺瘤的变化;HE染色检测组织病理学变化;RT-PCR和Western blot检测相关蛋白表达。结果:IOP可有效抑制SW620细胞增殖并诱导SW620细胞发生凋亡;NLRP3炎症小体和NF-κBp65磷酸化表达经IOP处理后呈增加趋势(P<0.05)。体内实验中发现,与模型组相比,IOP组小鼠体重有明显增加趋势,且结肠肿瘤和结肠病理组织形态得到改善;组织中IL-6和TNF-α基因表达降低,ASC、Caspase-1、NLRP3及NF-κBp65磷酸化蛋白水平显著增加(P<0.05)。结论:IOP抑制AOM/DSS诱导的小鼠CAC的发展,其机制可能与NF-κB和NLRP3信号途径的调控有关。
Objective:To determine whether Inonotus obliquus polysaccharide(IOP)can prevent occurrence and development of colitis-related colorectal cancer(CAC)by activating NF-κB and NLRP3 pathways.Methods:SW620 cells were treated with IOP,cell viability was measured by CCK-8,and levels of related genes,proteins and apoptosis related genes,proteins in NLRP3/NF-κB signaling pathway were detected by RT-PCR and Western blot,respectively.CAC mice model was induced by azoxymethane/dextran sodium sulfate(AOM/DSS),changes in body weight and colonic adenoma of mice were recorded;histopathological changes were detected by HE staining;expressions of related genes and proteins were detected by RT-PCR and Western blot.Results:IOP can effectively inhibit proliferation of SW620 cells;apoptosis of SW620 cell was induced;expressions of NLRP3 inflammasome and NF-κBp65 phosphorylation showed an increasing trend after IOP treatment(P<0.05).In vivo experiment,compared with model group,weight of mice in IOP group were significantly increased,and morphology of colon tumors and colon pathological tissues were also improved;expressions of IL-6 and TNF-αgenes in tissues were decrease,protein levels of ASC,Caspase-1,NLRP3 and NF-κBp65 phosphorylation were increased significantly(P<0.05).Conclusion:IOP inhibits development of CAC induced by AOM/DSS in mice,and its mechanism may be related to the regulation of NF-κB and NLRP3 signaling pathways.
作者
李佳威
曲超
陈一方
郑金娟
肖瑶
黄学洙
金丹(指导)
李芳芳(指导)
LI Jia⁃Wei;QU Chao;CHEN Yi⁃Fang;ZHENG Jin⁃Juan;XIAO Yao;HUANG Xue⁃Zhu;JIN Dan;LI Fang⁃Fang(Department of Immunology and Pathogenic Biology,Yanbian University Medical College,Yanji 133002,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2021年第4期437-442,共6页
Chinese Journal of Immunology
基金
国家自然科学基金项目(81160367,81860288)
