摘要
目的基于网络药理学方法预测华蟾素注射液的有效活性成分,以及治疗结直肠癌的分子作用机制。方法查阅并汇总国内外相关文献,查询PubChem数据库确定华蟾素注射液的活性成分,利用SwissTargetPrediction数据库检索活性成分靶点,运用GeneCards,TTD,DrugBank数据库查询结直肠癌的疾病靶点,利用Cytoscape 3.7.2软件绘制中药-活性成分-疾病靶点网络;应用String平台构建靶蛋白相互作用网络(PPI),并提取关键靶点,对关键靶点进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析,对核心靶点与主要活性成分进行分子对接。培养人克隆结肠腺癌Caco-2细胞,利用液质联用高分辨质谱仪考察1.0%,0.3%,0.1%华蟾素注射液对结直肠癌细胞中靶点蛋白的调节作用。结果华蟾素注射液的63个活性成分作用于25个结直肠癌的疾病靶点,信号转导及转录激活因子3(STAT3)、热激蛋白90α家族成员1(HSP90AA1)、表皮生长因子(EGFR)、激酶插入区域受体(KDR)、碳酸酐酶9(CA9)、Rho相关蛋白激酶1(ROCK1)、细胞间质上皮转换因子(c-MET)共7个关键靶基因参与结直肠癌的蛋白多糖、EGFR酪氨酸激酶抑制剂抵抗、非小细胞肺癌等信号通路。结论华蟾素注射液通过多活性成分、多靶点、多通路治疗结直肠癌。
Objective To predict the effective active ingredients of Huachansu Injection and its molecular mechanism in thetreatment of colorectal cancer(CRC)based on the network pharmacology.MethodsThe active ingredients of Huachansu Injectionwere determined by the relevant studies at home and abroad and the Pub Chem database.The targets of active ingredients weresearched by the Swiss Target Prediction database.The targets of CRC were searched by the Gene Cards,TTD and Drug Bank databases.The traditional Chinese medicine(TCM)-active ingredients-disease targets network was constructed by the Cytoscape 3.7.2 software.The protein-protein interaction(PPI)network was constructed and the key targets were extracted by the String platform.The gene ontology(GO)function analysis and the Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysisof the key targets were conducted.The molecular docking between the core targets and the main active ingredients was analyzed.The human colon adenocarcinoma Caco-2 cells were cultured,and the regulatory effects of 1.0%,0.3%and 0.1%of HuachansuInjection on the target proteins in CRC cells were investigated by the liquid chromatography tandem mass spectrometry with highresolution.ResultsA total of 63 active ingredients of Huachansu Injection acted on 25 CRC targets.Seven key target genesincluding signal transdution and activator of transcription 3(STAT3),heat shock protein 90αfamily member 1(HSP90AA1),epidermal growth factor receptor(EGFR),kinase insert domain containing receptor(KDR),carbonic anhydrase 9(CA9),Rho-associated protein kinase 1(ROCK1)and cellular-mesenchymal epithelial transition factor(c-MET)were involved in thesignaling pathways of CRC such as proteoglycan,EGFR tyrosine kinase inhibitor resistance and non-small cell lung cancer.ConclusionHuachansu Injection treat CRC through multiple active ingredients,multiple targets and multiple pathways.
作者
徐玲艳
于天怡
石美智
陈君君
邢婷玉
徐晓红
刘盈
韩永龙
张凤
姜波
XU Lingyan;YU Tianyi;SHI Meizhi;CHEN Junjun;XING Tingyu;XU Xiaohong;LIU Ying;HAN Yonglong;ZHANG Feng;JIANG Bo(Shanghai Jiao Tong University Affiliated Sixth People′s Hospital,Shanghai,China 201306;Changzheng Hospital,Second Military Medical University,Shanghai,China 200003)
出处
《中国药业》
CAS
2022年第19期26-35,共10页
China Pharmaceuticals
基金
上海市卫生健康委员会中医药传承和科技创新项目[ZYCC2019017]
上海市浦东新区科技发展基金民生科研专项[PKJ2019-Y04]
上海健康医学院附属医院2021年师资人才百人库项目[B3-0200-20-311008-02]。
关键词
华蟾素注射液
结直肠癌
化学活性成分
网络药理学
Huachansu Injection
colorectal cancer
chemical active ingredient
network pharmacology
