基于网络药理学和分子对接分析丰城鸡血藤治疗乳腺癌的分子靶点和机制

Mechanism of Callerya nitida var.hirsutissima in treatment of breast cancer based on network pharmacology

目的利用网络药理学、分子对接技术并进行体外实验验证,探讨丰城鸡血藤有效成分对应靶基因治疗三阴性乳腺癌(triple-negative breast cancer,TNBC)的作用机制。方法基于文献研究并结合数据库筛选得到丰城鸡血藤主要活性成分以及TNBC相关靶标寻找交集基因构建蛋白相互作用(PPI)网络图,根据相互关系大小筛选核心靶标。构建“中药-成分-靶点-疾病”核心靶标相互作用网络模型。将交集靶点进行基因GO功能分析和KEGG通路富集分析。最后将筛选出的成分与靶标进行分子对接以及体外实验验证。结果收集到丰城鸡血藤38个活性成分,相关潜在靶点388个,TNBC靶点3919个,丰城鸡血藤治疗TNBC靶点277个。主要作用于PIK3R1、PIK3CA、MAPK1、AKT1、SRC等多个靶标,在体外实验中可知,丰城鸡血藤三氯甲烷部位萃取物以及单体化合物木犀草素、白桦脂酸对细胞增殖均有一定的抑制作用。在给药浓度范围内各组均能抑制VEGFA、AKT、PIK3CA、CDK1、CDK4的表达。结论基于网络药理学和分子对接方法,对丰城鸡血藤治疗TNBC可能的靶标和信号通路进行探讨,并进行体外验证实验,进一步验证了网络药理学的预测。

Aim To explore the mechanism of action of the active ingredients of Callerya nitida var.hirsutissima corresponding to the target gene in the treatment of triple-negative breast cancer(TNBC),using network pharmacology,molecular docking technology and in vitro experimental verification.Methods Based on literature research and combined with database screening,the main active components of Callerya nitida var.hirsutissima and the related targets of TNBC were obtained.Intersection genes were found to construct a protein interaction(PPI)network diagram,and core targets were screened according to the size of the correlation.A core target interaction network model of“Traditional Chinese Medicine-Ingredients-Targets-Disease”was constructed.The intersection targets were analyzed for gene GO function and KEGG pathway enrichment analysis.Finally,molecular docking and in vitro experimental verification of the selected components and the target were carried out.Results A total of 38 active components of Callerya nitida var.hirsutissima were collected,as well as 388 related potential targets,3919 TNBC targets,and 277 Callerya nitida var.hirsutissima therapeutic targets for TNBC.It mainly acted on multiple targets such as PIK3R1,PIK3CA,MAPK1,AKT1,SRC,etc.In in vitro experiments,it could be seen that the chloroform fraction of Callerya nitida var.hirsutissima and the monomer compounds luteolin and betulin had certain inhibitory effects on cell proliferation.All groups could inhibit the expression of VEGFA,AKT,PIK3CA,CDK1,CDK4 within the range of administration concentration.Conclusions Based on network pharmacology and molecular docking methods,this study explores the possible targets and signaling pathways of Callerya nitida var.hirsutissima in the treatment of TNBC,and conducts in vitro verification experiments to further verify the prediction of network pharmacology.