沙参麦冬汤通过调控PI3K-AKT通路及JUN表达治疗食管癌  

Mechanism of Shashen Maidong decoction in treating esophageal cancer by regulating PI3K-AKT pathway and JUN expression

作　　者：陈田田 杨晶晶[1] 徐佳倩 储博文 陈冰[1] 董博翰[1] 余方流[1] CHEN Tiantian;YANG Jingjing;XU Jiaqian;CHU Bowen;CHEN Bing;DONG Bohan;YU Fangliu(Department of Microbiology and Immunology,Wannan Medical College,Wuhu 241002,Anhui,China)

机构地区：[1]皖南医学院医学微生物学与免疫学教研室,安徽芜湖241002

出　　处：《皖南医学院学报》2025年第1期11-15,共5页Journal of Wannan Medical College

基　　金：安徽省高校自然科学研究项目(2023AH040263;2022AH051235)。

摘　　要：目的:采用网络药理学与实验验证探究沙参麦冬汤治疗食管癌的作用靶点与相关机制。方法:检索TCMSP和SymMap数据库获取沙参麦冬汤的化学成分与作用靶点,借助Gene Cards数据库获取食管癌相关作用靶点,运用Venny 2.1.0平台获取沙参麦冬汤复方与食管癌疾病的交集靶点,利用STRING数据库和Cytoscape 3.9.1软件构建蛋白相互作用(PPI)网络,使用DAVID数据库进行GO功能富集和KEGG通路富集分析。通过GEPIA 2.0对核心基因氨基末端激酶JUN进行免疫浸润分析。采用分子对接技术进行验证,建立食管癌小鼠移植瘤模型,药物干预4周后,观察小鼠肿瘤体积变化,采用qRT-PCR检测脾脏中磷脂酰肌醇3-激酶(PI3K)、蛋白激酶B(AKT)的mRNA表达水平。结果:沙参麦冬汤抑制食管癌小鼠肿瘤的生长(P<0.01);经数据分析得到沙参麦冬汤活性成分67个,对应靶点1190个,食管癌相关靶点446个,药物与疾病交集靶点56个,其中JUN为核心靶点。主要富集于PI3K-AKT信号通路。相关分子对接显示核心靶点与其所对应的活性成分均有较好的结合能力(结合能<-5 J/moL),核心基因JUN高表达与效应性的Treg细胞、耗竭性T细胞浸润均呈正相关(P<0.01);与模型组相比,PI3K、AKT的mRNA表达水平均降低(P<0.05)。结论:沙参麦冬汤对食管癌具有明显的治疗效果,其主要机制可能与抑制PI3K-AKT信号通路及JUN的表达并旁路激活机体抗肿瘤免疫密切相关。Objective:To investigate the targets and related mechanisms of Shashen Maidong decoction in treating esophageal cancer via network pharmacology and experimental validation.Methods:TCMSP and SymMap databases were searched to obtain the chemical components and targets of Shashen Maodong decoction,t he esophageal cancer-related targets were obtained through GeneCards database,and the intersection targets of Shashen Maidong decoction compound and esophageal cancer were identified through Venny 2.1.0 platform.The protein interaction(PPI)network was constructed using STRING database and Cytoscape 3.9.1 software,and GO functional enrichment and KEGG pathway enrichment analyses were performed by means of DAVID database.Immune infiltration analysis of the core gene amino-terminal kinases JUN was carried out via GEPIA 2.0 web server.Then molecular docking technology was used for verification of the data obtained.A xenograft model of esophageal cancer was established into mice,in which tumor volume changes were observed after 4 weeks of drug intervention.The mRNA expression levels of phosphoinositide-3 kinase(PI3K)andprotein kinase B(AKT)in the spleen were determined by quantitative real-time PCR.Results:Shashen Maidong decoction significantly inhibited the growth of tumors in mice with esophageal cancer(P<0.01).Data analysis of the decoction revealed 67 active ingredients,1190 corresponding targets,446 targets related to esophageal cancer,and 56 targets of drug and disease intersection,among which JUN was the core target,and mainly enriched in the PI3K-AKT signaling pathway.The docking of related molecules showed that the core target had better binding ability with its corresponding active components(binding energy<-5 J/moL).High expression of the core gene JUN was positively associated with effector Treg cells and depletive T cell infiltration(P<0.01).mRNA level in the PI3K and AKT was decreased compared to the model group(P<0.05).Conclusion:Shashen Maidong decoction possesses obvious therapeutic effect on esophageal canc

关 键 词：沙参麦冬汤 食管癌 网络药理学 磷脂酰肌醇3-激酶-蛋白激酶B 氨基末端激酶 

分 类 号：R285[医药卫生—中药学] R392.1[医药卫生—中医学] R-332