藤梨根调控IL-17信号通路影响胃癌细胞迁移与凋亡  

Tengligen(Radix Actinidiae Chinensis)Affecting Gastric Cancer Cell Migration and Apoptosis by Modulating IL-17 Signaling Pathway

作　　者：曹洋 董博[2] 刘莹 岳广欣[4] 申力 CAO Yang;DONG Bo;LIU Ying;YUE Guangxin;SHEN Li(Shaanxi University of Traditional Chinese Medicine,Xianyang Shaanxi China 712046;Red Cross Hospital,Xi′an Jiaotong University,Xi′an Shaanxi China 710054;Institute of Traditional Chinese Medicine,China Academy of Chinese Medical Sciences,Beijing China 100700;Institute of Basic Theory of Chinese Medicine,China Academy of Chinese Medical Sciences,Beijing China 100700)

机构地区：[1]陕西中医药大学,陕西咸阳712046 [2]西安交通大学附属红会医院,陕西西安710054 [3]中国中医科学院中药研究所,北京100700 [4]中国中医科学院中医基础理论研究所,北京100700

出　　处：《中医学报》2025年第3期465-473,共9页Acta Chinese Medicine

基　　金：中国中医科学院科技创新工程“中药药性学学科”重大攻关项目(CI2021A03809);国家自然科学基金面上项目(82074398);中央级公益性科研院所基本科研业务费专项资金项目(YZX-202407);中国中医科学院科技创新工程项目中医理论传承与创新专项项目(KYG-202406)。

摘　　要：目的:采用网络药理学和细胞实验探讨藤梨根(Tengligen,TLG)调控白细胞介素(interleukin,IL)-17信号通路治疗胃癌的作用机制。方法:通过中医药整合药理学研究平台(Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine,TCMIP)筛选藤梨根的活性成分和靶点,借助GeneCards、Uniprot数据库查找胃癌的靶点,并利用Venny 2.1.0获取两者的交集靶点。将交集靶点导入STRING数据库,构建蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络。通过Cytoscape 3.10.1软件进行网络拓扑学分析,根据Degree值筛选核心靶点。利用DAVID数据库进行基因本体(Gene Ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析。将25只SD大鼠随机分为空白组5只和藤梨根组(0.3125 g·kg^(-1))20只,连续灌胃5 d,制备空白血清和含药血清。将HGC-27细胞分为对照组、空白血清组、12%藤梨根含药血清组(TLG-L)、24%藤梨根含药血清组(TLG-M)及48%藤梨根含药血清组(TLG-H),采用Transwell实验检测细胞的迁移能力,流式细胞仪检测细胞凋亡,ELISA法检测上清液中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、IL-6、IL-1β含量,Western blot法检测IL-17A、核转录因子-κB(nuclear transcription factor-κB,NF-κB)、基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)蛋白表达水平。结果:藤梨根靶点159个,胃癌靶点1010个,两者的交集靶点95个。藤梨根治疗胃癌的核心靶点包括肿瘤蛋白p53(tumor protein 53,TP53)、IL-6、B淋巴细胞瘤-2(B-cell lymphoma-2,BCL2)、MMP-9、TNF等。KEGG分析得到123条通路,包括IL-17信号通路、PI3K-Akt信号通路、HIF-1信号通路等。与空白血清组比较,TLG-L组、TLG-M组、TLG-H组细胞迁移数目减少、细胞凋亡率升高(P<0.01)。与对照组比较,空白血清组细胞上清液中TNF-α、IL-6含量升高(P<0.01)。与空白血清组比较,TLG-L组、TLG-M组、TLG-H组细胞�Objective:To explore the mechanism of action of Tengligen(TLG)in regulating interleukin(IL)-17 signaling pathway in treatment of gastric cancer by using network pharmacology and cellular experiments.Methods:The active components and targets of Tengligen(TLG)were screened by Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine(TCMIP),and the active components and targets of TLG were identified by GeneCards,Uniprot database to find the targets of gastric cancer,and utilized Venny 2.1.0 to obtain the intersecting targets of the two.The intersecting targets were imported into the STRING database to construct a protein-protein interaction(PPI)network.The network topology was analyzed by Cytoscape 3.10.1 software,and the core targets were screened according to the Degree value.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed using the DAVID database.Twenty-five SD rats were randomly divided into 5 in the blank group and 20 in the Tengligen group(0.3125 g·kg^(-1)),and the blank serum and drug-containing serum were prepared by consecutive gastric gavage for 5 d.The cells of HGC-27 cells were divided into control cells and HGC-27 cells.Tumor necrosis factor-α(TNF-α),IL-6 and IL-1βwere detected in the supernatant with ELISA,and IL-17A,nuclear transcription factor-κB(NF-κB),matrix metalloproteinase-9(matrix-κB),IL-1β,NF-κB,matrix metalloproteinase-9(MMP-9)protein expression level were detected with Western blot.Results:There were 159 targets of Garcinia cambogia,1010 targets of gastric cancer,and 95 intersecting targets of both.The core targets of Tengligen for gastric cancer treatment included tumor protein 53(TP53),IL-6,B-cell lymphoma-2(BCL2),MMP-9,TNF,etc.KEGG analysis yielded 123 pathways,including IL-17 signaling pathway,PI3K-Akt signaling pathway,HIF-1 signaling pathway,etc.Compared with the blank serum group,the number of cell migration was reduced,and the apoptosis rate was increased in the TLG-L,TLG-M and TLG-H groups(P<0.01).

关 键 词：藤梨根 胃癌 HGC-27细胞 IL-17通路 网络药理学 槲皮素 细胞迁移 细胞凋亡 

分 类 号：R285.5[医药卫生—中药学]