摘要
目的利用网络药理学探析祛瘀解毒方治疗结直肠癌的机制。方法从中药系统药理学分析平台收集组方药物的活性成分及靶点,与Genecards网站收集的CRC相关靶点取交集后,筛选出祛瘀解毒方治疗CRC的潜在靶点,利用Cytoscape软件绘制中药-活性成分-靶点网络图并分析出该网络的核心成分,利用STRING数据库和Cytoscape软件构建靶蛋白互作网络并分析出该网络的核心靶点,利用R语言中clusterProfiler包对基因进行基因本体分子功能和京都基因与基因组百科全书通路富集分析,最后通过分子对接探讨核心成分与核心靶点之间的相互作用情况。结果祛瘀解毒方治疗CRC的核心成分可能为槲皮素、木犀草素、汉黄芩素,核心治疗靶点可能为TP53、AKT1和ALB,与CRC相关的通路涉及细胞增殖、细胞凋亡、血管生成、内分泌、肿瘤免疫、MicroRNA和耐药性等方面。分子对接表明AKT1、ALB与槲皮素、木犀草素、汉黄芩素相互作用较强。结论该研究表明祛瘀解毒方治疗CRC的多成分、多靶点、多通路作用机制,可为今后阐明祛瘀解毒方治疗CRC的具体机制提供思路。
Objective To explore the pharmacological mechanism of Quyu Jiedu Prescription(祛瘀解毒方)in the treatment of colorectal cancer(CRC)based on network pharmacology.Methods Both active ingredients of Quyu Jiedu Prescription as well as corresponding targets from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and CRC-related genes retrieved from the Genecards website were combined,and overlapping targets regarded as the potential targets of Quyu Jiedu Prescription for CRC were acquired.A herb-active ingredient-target network was built and analyzed for key ingredients.By the STRING database and the Cytoscape software,the protein-protein interaction(PPI)network was constructedand studied for key targets.Furthermore,based on cluster Profiler package in R-3.6.1 project,Gene Ontology(GO)molecular function analysis and Kyoto encyclopedia of genes and gnomes(KEGG)pathway analysis were performed.Finally,relations between key ingredients and key genes were investigated by the method of molecular docking.Results Key ingredients of Quyu Jiedu Prescription for CRC may be quercetin,luteolin and wogonin while key therapeutic targets may be tumor protein p53(TP53),protein kinase B(PKB or AKT1)and albumin(ALB).CRC-related pathways involved cell proliferation,apoptosis,angiogenesis,endocrine,tumor immunity,MicroRNA,drug resistance and so on.Molecular docking revealed a reliable interaction of AKT1,ALB and quercetin,luteolin and wogonin.Conclusion The study indicates that mechanisms of Quyu Jiedu Prescription for CRC are likely to involve multi-ingredient,multi-target and multi-pathway,which could present ideas for clarifying concrete mechanism of the therapeutic effect of Quyu Jiedu Prescription on CRC in the future.
作者
何灿封
孙玲玲
林丽珠
HE Canfeng;SUN Lingling;LIN Lizhu(The First Clinical Medical College of Guangzhou University of Chinese Medicine,Guangzhou 510405,Guangdong,China;The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,Guangdong,China)
出处
《辽宁中医杂志》
CAS
2021年第7期160-165,258-259,共8页
Liaoning Journal of Traditional Chinese Medicine
基金
广州市科技计划项目(201904010396)
关键词
祛瘀解毒方
结直肠癌
网络药理学
KEGG通路
分子对接
Quyu Jiedu Prescription(祛瘀解毒方)
colorectal cancer
network pharmacology
KEGG pathway
molecular docking
