草黄口蘑多糖对S180荷瘤小鼠抗肿瘤活性分子机制研究  

Molecular mechanism of anti-tumor activity of polysaccharide from Tricholoma lascivum(Fr.)Gillet on S180 tumor-bearing mice

作　　者：赵倪慧 蒋琳 张丁 段江波 丁祥 侯怡铃[1] ZHAO Nihui;JIANG Lin;ZHANG Ding;DUAN Jiangbo;DING Xiang;HOU Yiling(Key Laboratory of Southwest China Wildlife Resources Conservation(Ministry of Education),College of Life Sciences,China West Normal University,Nanchong 637009,China;College of Environmental Science and Engineering,China West Normal University,Nanchong 637009,China)

机构地区：[1]西华师范大学生命科学学院,西南野生动植物资源保护教育部重点实验室,四川南充637009 [2]西华师范大学环境科学与工程学院,四川南充637009

出　　处：《食品与发酵工业》2024年第11期27-37,共11页Food and Fermentation Industries

基　　金：四川省科技厅应用基础面上项目(2022NSFSC0107);四川省科技厅农业科技成果转化资金项目(2022NZZJ0003);四川省转移支付科技成果转移转化示范项目(22ZYZFSF0009;23ZHSF0082);农业农村部农业微生物资源收集与保藏重点实验室开放课题(KLMRCP2021-01)。

摘　　要：多糖作为口蘑属真菌的主要功能成分之一,具有免疫调节、抗氧化及抗肿瘤等活性。为明确草黄口蘑多糖的结构特征及其对S180荷瘤小鼠抗肿瘤活性相关分子机制,该研究以草黄口蘑子实体经热水浸提法提取的草黄口蘑多糖[Tricholoma lascivum (Fr.)Gillet polysaccharide,TLG-1]为实验材料,初步解析TLG-1结构,以S180荷瘤小鼠为模型检测体内抗肿瘤活性,并采用转录组测序技术对S180肿瘤组织总RNA进行测序分析。结果表明,TLG-1重均分子质量为13 442 Da,由木糖、甘露糖、葡萄糖和半乳糖4种单糖组成,其比例为1.57∶1.45∶2.84∶4.14。TLG-1可显著抑制荷瘤小鼠S180肿瘤的生长(P<0.01),抑瘤率为53.8%。转录组测序分析显示,TLG-1能显著上调mt-Co1、Prlr、Foxa1以及下调Pitx2、Rplp1、Eef1a1及Lgals1等基因,影响S180肿瘤细胞的代谢途径,调控细胞周期并抑制上皮间质转化过程。基因本体富集分析表明,TLG-1可激活细胞因子介导的信号通路,引发细胞免疫。京都基因与基因组百科全书富集分析显示,在Jak-STAT信号通路中的Il21、Il12rb2、Il12b、Il2ra、Il2rb、Il2rg、Il15ra和Ifng等基因显著上调,通过转换肿瘤相关巨噬细胞表型及分泌干扰素-γ等,增强小鼠抗肿瘤免疫应答。该研究结果为草黄口蘑多糖的开发和利用提供了一定的理论基础。As one of the main functional components of Tricholoma,polysaccharides have activities such as immune regulation,antioxidant and anti-tumor effects.To clarify the structure and the molecular mechanisms of anti-tumor activity of polysaccharide from Tricholoma lascivum(Fr.)Gillet on S180 tumor-bearing mice,the Tricholoma lascivum(Fr.)Gillet polysaccharide(TLG-1)extracted from the fruiting body of Tricholoma lascivum(Fr.)Gillet by hot water extraction method was used as the experimental material,the structure of TLG-1 was preliminarily analyzed,S180 tumor bearing-mice were used as models to detect anti-tumor activity in vivo,the total RNA of S180 tumor tissue was also sequenced using RNA sequencing.Results showed that TLG-1 had the weight-average molecular weight of 13442 Da and was composed of xylose,mannose,glucose,and galactose in a ratio of 1.57∶1.45∶2.84∶4.14.TLG-1 could significantly inhibit the growth of S180 tumors in mice(P<0.01),with a tumor inhibition rate of 53.8%.Transcriptome sequencing analysis showed that TLG-1 could significantly up-regulate genes such as mt-Co1,Prlr,Foxa1,and down-regulate genes such as Pitx2,Rplp1,Eef1a1,and Lgals1,affecting the metabolic pathways of S180 tumor cells,regulating the cell cycle,and inhibiting epithelial-mesenchymal transition process.Gene ontology enrichment analysis showed that TLG-1 could activate cytokine-mediated signaling pathways and trigger cellular immunity.Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that genes such as Il21,Il12rb2,Il12b,Il2ra,Il2rb,Il2rg,Il15ra,and Ifng in the Jak-STAT signaling pathway were significantly up-regulated.TLG-1 could enhance the anti-tumor immune response of mice by transforming tumor-associated macrophage phenotype,and secreting interferon-γ.The results could provide a theoretical basis for the development and utilization of TLG-1.

关 键 词：草黄口蘑多糖TLG-1 抗肿瘤 S180 转录组测序技术 JAK-STAT信号通路 

分 类 号：TS201.4[轻工技术与工程—食品科学] R285.5[轻工技术与工程—食品科学与工程]