基于网络药理学分析皂角刺对人结肠癌HCT116细胞增殖的抑制作用  

Analysis of the inhibitory effect of soapberry thorn on the proliferation of human colon cancer HCT116 cells based on network pharmacology

作　　者：吴栋娟 何春华 范耀华 Wu Dongjuan;He Chunhua;Fan Yaohua(Department of Oncology Surgery,Second Affiliated Hospital of Jiaxing University Second Affiliated Hospital of Jiaxing University,Jiaxing 314000,China)

机构地区：[1]嘉兴大学附属第二医院肿瘤科,嘉兴314000

出　　处：《中华实验外科杂志》2024年第11期2527-2530,共4页Chinese Journal of Experimental Surgery

基　　金：浙江省医药卫生科技计划项目(2021KY1118)。

摘　　要：目的:基于网络药理学、分子对接及体外实验的方法,探讨皂角刺对结肠癌作用的潜在机制。方法:皂角刺的药物靶点来源于中药系统药理学分析平台(TCMSP)。结肠癌相关疾病靶标来源于人类基因综合分析数据库(Genecards)和人类孟德尔遗传病的数据库(OMIM)。通过维恩图(Venn)获取两者交集靶点,此外,通过基因本体论(GO)和京都基因和基因组通路(KEGG)和网络分析,进一步探索潜在的机制。通过定量聚合酶链反应(RT-qPCR)验证皂角刺对结肠癌相关靶蛋白影响的可靠性。计量资料以均数±标准差(x±s)表示,两组间比较行独立样本t检验,多组间比较行方差分析。结果:将皂角刺在TCMSP数据库进行检索,筛选出活性成分所对应的不重复靶点共113个;在Genecards和OMIM数据库中筛选出201个结肠癌相关靶点;将上述皂角刺药物靶点与结肠癌相关疾病靶点通过微生信在线绘图工具进行韦恩图的绘制,筛选出药物疾病共同靶点23个;将获得的23个治疗靶点通过PPI网络构建及富集分析筛选出结肠癌核心靶点如下:基质金属蛋白酶(MMP)-1、MMP-9、网状内皮增生病毒癌基因同源物A重组蛋白(RELA)和前列腺素内过氧化物合成酶2(PTGS2)。体外细胞实验结果表明皂角刺给药组HTC116细胞增殖水平明显高于对照组(180.72±16.51比110.20±14.68,t=0.096,P<0.05);采用50μmol/L皂角刺处理HTC116细胞24 h后,药物处理组MMP-1、MMP-9、RELA和PTGS2表达水平明显低于对照组(120.62±72.33、116.62±73.21、130.57±69.46、124.15±58.35比152.48±69.98、160.31±67.54、171.25±63.62、177.03±70.72,t=0.082、0.076、0.081、0.079,P<0.05)。结论:皂角刺可抑制结肠癌HCT116细胞增殖,其作用机制可能与改善炎症反应有关。Objective Based on network pharmacology,molecular docking,and in vitro experiments,this study aims to reveal the potential mechanisms of Gleditsiae Spina in the treatment of colorectal cancer.Methods The drug targets of soapberry thorn are derived from the Traditional Chinese Medicine Systems Pharmacology(TCMSP)platform.The targets of colon cancer-related diseases are sourced from The Human Gene Database(Genecards)and the Online Mendelian Inheritance in Man(OMIM)database.Obtain the intersection targets of the two through Venn diagram,and further explore potential mechanisms through Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes KEGG,and network analysis.Verify the reliability of the effect of soapberry thorn on colon cancer-related target proteins through in vitro proliferation experiments(RT-qPCR).Use one-way ANOVA for inter group comparison.The measurement data is expressed as mean±standard deviation(x±s),and independent-samples t-test is used for comparison between two groups,while analysis of variance is used for comparison between multiple groups.Results Retrieve soapberry thorns from the TCMSP database and screen out 113 non duplicated targets corresponding to the active ingredients;201 colon cancer-related targets were screened from Genecards and OMIM databases;The above-mentioned soapberry thorn drug targets and colon cancer-related disease targets were plotted on a Venn diagram using a WeChat online drawing tool,and 23 common drug disease targets were screened;The 23 therapeutic targets obtained were selected through PPI network construction and enrichment analysis to identify the core targets of colon cancer as follows:matrix metalloproteinase(MMP)-1,MMP-9,reticuloendotheliosis virus oncogene homolog A recombinant protein(RELA),and prostaglandin endoperoxide synthase 2(PTGS2).The results of in vitro cell experiments showed that the proliferation level of HTC116 cells in the soapberry thorn treated group was significantly higher than that in the control group and formed a dose-dependent rela

关 键 词：皂角刺 结肠癌 网络药理学 分子对接 实验验证 

分 类 号：R285[医药卫生—中药学]