基于网络药理学解析青蒿素治疗结直肠癌的分子机制  

Analysis of the Molecular Mechanism of Artemisinin in the Treatment of Colorectal Cancer Based on Network Pharmacology

作　　者：杨高明 张靖宜 王梦琦 董思进 王丹[1] 周燕红[1] YANG Gao-ming;ZHANG Jing-yi;ZHOU Yan-hong(Xianning Medical College,Hubei University of Science and Technology,Xianning Hubei 437100,China)

机构地区：[1]湖北科技学院医学部,湖北咸宁437100

出　　处：《湖北科技学院学报（医学版）》2023年第1期33-38,共6页Journal of Hubei University of Science and Technology(Medical Sciences)

基　　金：2021年度湖北省省级大学生创新创业训练计划项目(S202110927026);2021年度咸宁市级科技计划立项项目(2021ZRKX025)。

摘　　要：目的基于网络药理学解析青蒿素治疗结直肠癌的分子机制。方法通过TCMSP、OMIM等数据库对青蒿素的作用靶点及结直肠癌的疾病靶点进行检索筛选,将药物成分靶点与疾病靶点取交集,采用STRING数据库、Cytoscape3.8.2软件及相关插件构建蛋白相互作用网络图,利用DAVID对核心靶点进行GO富集分析、KEGG通路富集分析。采用AutoDock Vina进行分子对接。结果共筛选获得青蒿素活性成分22个,作用靶点499个,将药物成分靶点与青蒿素疾病靶点取交集共获得靶点12个,构建PPI网络,经拓扑及聚类分析后获得TP53、EGFR、CCND1、CDKN2A、AKT1和RB1等关键靶点。GO分析显示,青蒿素对结直肠癌的作用机制涉及从RNA聚合酶Ⅱ启动子转录、蛋白质磷酸化、对雌激素的反应等过程。KEGG通路富集为Pathways in cancer通路等;分子对接结果显示,关键靶点TP53与活性成分青蒿素结合能为-4.0Kcal/mol;免疫浸润结果显示TP53表达与CD8^(+)T Cell呈正相关。结论青蒿素治疗结直肠癌具有多靶点、多通路的特点,可能通过关键靶点TP53影响凋亡过程、细胞增殖等实现对结直肠癌的治疗作用。Objective To analyze the molecular mechanism of artemisinin in the treatment of colorectal cancer based on network pharmacology.Methods Action targets and colorectal cancer disease targets of artemisinin were searched and screened on database such as TCMSP,OMIM,or related plugins to construct a protein interaction network map.DAVID was uses to perform GO enrichment analysis and KEGG pathway enrichment analysis on core targets.Molecular docking was performed using AutoDock Vina.Results A total of 22 active components of artemisinin were screened and 499 targets were obtained.A total of 12 targets were obtained by taking the intersection of drug component targets and artemisinin disease targets.A PPI network was constructed.Key targets such as TP53,EGFR,CCND1,CDKN2A,AKT1 and RB1 were obtained after topological and cluster analysis.GO analysis showed that the mechanism of action of artemisinin on colorectal cancer involved processes such as transcription from the RNA polymeraseⅡpromoter,protein phosphorylation,and response to estrogen.The KEGG pathway was enriched into the Pathways in cancer pathway,etc.The molecular docking results showed that the binding energy of the key target TP53 and the active ingredient artemisinin was-4.0 Kcal/mol.The immune infiltration results showed that the expression of TP53 was positively correlated with CD8^(+)T Cells.Conclusion Artemisinin in the treatment of colorectal cancer has the characteristics of multiple targets and multiple pathways.Artemisinin may affect the process of apoptosis and cell proliferation through the key target TP53 to achieve the therapeutic effect on colorectal cancer.

关 键 词：青蒿素 结直肠癌 网络药理学 分子机制 

分 类 号：R735[医药卫生—肿瘤]