摘要
目的采用网络药理学和分子对接技术分析大血藤-败酱草抗结直肠癌的分子机制。方法首先采用公共数据库挖掘大血藤-败酱草的相关活性成分和靶点以及结直肠癌的相关靶点,筛选出结直肠癌治疗的潜在靶点。然后进行中药-成分-靶点网络和蛋白质-蛋白质相互作用(PPI)网络分析,采用基因本位(GO)和京都基因与基因组百科全书(KEGG)通路富集分析治疗结直肠癌涉及的分子功能、细胞成分、生物过程及相关通路,并构建靶点-通路网络,筛选结直肠癌治疗的关键靶点。最后采用分子对接技术评价关键成分与靶点的亲和力。结果大血藤-败酱草治疗结直肠癌的成分主要是芹菜素、槲皮素、大黄素等,涉及促分裂原活化的蛋白激酶(MAPK)1、MAPK3、蛋白激酶B丝氨酸/苏氨酸激酶1(AKT1)、磷脂酰肌醇-4,5二磷酸3-激酶催化亚单位α(PIK3CA)等多个靶点。GO分析主要富集于蛋白质磷酸化、蛋白激酶活性、转录调控复合物等方面;KEGG通路富集分析显示,癌症通路、表皮生长因子受体(EGFR)-酪氨酸激酶抑制剂(TKI)耐药性、磷脂酰肌醇-3-羟激酶(PI3K)/蛋白激酶B(AKT)信号通路等均是结直肠癌治疗的重要通路。芹菜素、槲皮素、大黄素与MAPK1、MAPK3和PIK3CA均有强烈亲和力,与AKT1亲和力较好,芹菜素-PIK3CA、槲皮素-MAPK1、大黄素-PIK3CA能够形成相对稳定的复合物。结论大血藤-败酱草可能通过抑制MAPK1、MAPK3、和PIK3CA靶蛋白的表达,通过调控PI3K/AKT、MAPK信号通路介导的细胞增殖、迁移和凋亡等过程发挥抗结直肠癌作用。
Objective To analyze the anti-colorectal cancer action mechanism of Dahurian-Patrinia based on network pharmacology and molecular docking.Method Firstly,the public database was used to mine the relevant active ingredients and targets of Dahurian-Patrinia and the related targets of colorectal cancer,and screened out potential targets for colorectal cancer treatment.Then the traditional Chinese medicine-component-target network and protein-protein interaction(PPI)network were constructed.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyzes were used to predict the molecular functions,cellular components,biological processes,and related pathways involved in the treatment of colorectal cancer.Thereafter,a target-pathway network was constructed to screen key targets for colorectal cancer treatment.Finally,molecular docking technology was used to evaluate the affinity between the key components and the target.Result The active components of dahurian-patrinia for the treatment of colorectal cancer were apigenin,quercetin,emodin,etc.,involving mitogen-activated protein kinase(MAPK)1,MAPK3,and protein kinase B serine/threonine kinase 1(AKT1),phosphatidylinositol-4,5-phosphate 3-kinase catalytic subunitα(PIK3CA),and other targets.GO analysis was mainly enriched in protein phosphorylation,protein kinase activity,transcriptional regulatory complexes,etc.KEGG pathway enrichment analysis showed that cancer pathways,epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitor(TKI)resistance,phosphoinositide 3-hydroxy kinase(PI3K)/protein kinase B(AKT)signaling pathways were important pathways in colorectal cancer treatment.Apigenin,quercetin,and emodin all had strong affinity with MAPK1,MAPK3,and PIK3CA,and had better affinity with AKT1.Apigenin-PIK3CA,quercetin-MAPK1,and emodin-PIK3CA could form relatively stable complexes.Conclusion Dahurian-Patrinia may exert anti-colorectal cancer effects by inhibiting MAPK1,MAPK3,PIK3CA,AKT1 expression and regulating cell proliferation,migration and apoptosis mediated by PI3K-AKT and MAPK signaling pathway.
作者
张文翠
周静
郝淑兰
刘丽坤
ZHANG Wencui;ZHOU Jing;HAO Shulan;LIU Likun(Shanxi Provincial Institute of Traditional Chinese Medicine,Taiyuan 030012,Shanxi,China;Department of Oncology,Shanxi Traditional Chinese Medical Hospital,Taiyuan 030012,Shanxi,China)
出处
《癌症进展》
2023年第18期2020-2025,2029,共7页
Oncology Progress
基金
国家中医临床研究基地(国中医药科技函[2018]131号)
山西省医学科技创新团队建设项目(2020TD04)
山西省中医临床医学研究中心科研项目(LCYJZX202106)。
关键词
网络药理学
分子对接
大血藤
败酱草
结直肠癌
network pharmacology
molecular docking
Dahurian
Patrinia
colorectal cancer
