基于网络药理学研究泽泻醇B抑制非小细胞肺癌的作用及机制  

Study on inhibitory effect of alisol B on non-small cell lung cancer based on network pharmacology and its mechanism

作　　者：向柳燕 王文萱 顾斯萌 张晓倩 李陆垚 李玉倩 王媛茹 雷琪琪 杨雪[1] 曹亚军[1] 李学军 XIANG Liu-yan;WANG Wen-xuan;GU Si-meng;ZHANG Xiao-qian;LI Lu-yao;LI Yu-qian;WANG Yuan-ru;LEI Qi-qi;YANG Xue;CAO Ya-jun;LI Xue-jun(Dept of Pharmacology and Key Laboratory of Xinjiang Phytomedicine Resource and Utilization,Ministry of Education,Shihezi University,Shihezi Xinjiang 832002,China;Dept of Pharmacology,School of Basic Medical Sciences,Peking University,Beijing 100191,China;Dept of Pharmacology,School of Pharmacy,Xinjiang Medical University,Urumuqi 830017,China)

机构地区：[1]石河子大学药理学教研室,新疆植物药资源与利用教育部重点实验室,新疆石河子832002 [2]北京大学基础医学院药理学教研室,北京100191 [3]新疆医科大学药学院药理学教研室,新疆乌鲁木齐830017

出　　处：《中国药理学通报》2024年第12期2375-2384,共10页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 82073878,81874318)。

摘　　要：目的探究泽泻醇B(alisol B)抑制非小细胞肺癌(non-small cell lung cancer,NSCLC)的潜在基因与机制。方法通过CCK-8和Transwell检测泽泻醇B对NSCLC细胞的增殖及迁移作用。通过TCGA和化合物基因预测数据库收集NSCLC和泽泻醇B的基因,并获得二者交集基因。应用String数据库构建蛋白-蛋白分子相互作用(protein protein interaction,PPI)网络,筛出前20的节点,运用R语言筛出与NSCLC预后相关的蛋白,并获得二者交集;通过KEGG和GO富集分析及相关基因与免疫细胞关系分析探究泽泻醇B作用于NSCLC的潜在机制,并通过细胞水平实验验证。结果泽泻醇B抑制NSCLC细胞的细胞活力和迁移能力。通过网络药理学分析确定5个重要基因:CCNE1,CDK1,COL1A1,COL1A2,COL3A1;细胞实验结果显示泽泻醇B下调NSCLC细胞中Cyclin E1、CDK1和COL1A2的表达。此外,泽泻醇B可抑制巨噬细胞中COL1A2和M2型巨噬细胞标志物CD206的表达。结论泽泻醇B可能通过下调CDK1和Cyclin E1抑制肿瘤细胞增殖,并可能通过抑制COL1A2影响巨噬细胞功能,从而调控肿瘤免疫微环境,对NSCLC产生抑制作用。Aim To explore the potential genes and mechanism of alisol B in the treatment of non-small cell lung cancer(NSCLC).Methods The proliferation and migration of NSCLC cells were detected by CCK-8 and Transwell.Genes of NSCLC and alisol B were collected through TCGA and compound gene prediction database,and their intersection genes were obtained.The network of protein-protein interaction(PPI)was constructed by using String database,and the top 20 key nodes were screened out,and the prognosis-related proteins related to the prognosis of NSCLC were screened out by using R language,and the intersection of them was obtained.The potential mechanism of alisol B on NSCLC was explored by KEGG and GO enrichment analysis and the relationship between related genes and immune cells,which was verified by cell-level experiments.Results Alisol B inhibited the cell activity and migration ability of NSCLC cells.Five important genes were identified by network pharmacological analysis:CCNE1,CDK1,COL1A1,COL1A2 and COL3A1.The results of cell experiment showed that alisol B down-regulated the expression of Cyclin E1,CDK1 and COL1A2 in NSCLC cells.In addition,alisol B could inhibit the expression of COL1A2 and M2 macrophage marker CD206 in macrophages.Conclusions Alisol B may inhibit the proliferation of tumor cells by down-regulating CDK1 and Cyclin E1,and may affect the function of macrophages by inhibiting COL1A2,thus regulating the tumor immune microenvironment and inhibiting NSCLC.

关 键 词：泽泻醇B NSCLC 天然药物 网络药理学 肿瘤微环境 肿瘤相关巨噬细胞 

分 类 号：R284.1[医药卫生—中药学] R319[医药卫生—中医学] R329.24R734.2