基于网络药理学探讨益肾清肝方逆转乳腺癌内分泌治疗耐药机制  

Exploring the Mechanism of Yishen Qinggan Prescription to Reverse Endocrine Therapy Resistance of Breast Cancer Based on Network Pharmacology

作　　者：桂越蓉 王烁 董军 周彤 王丹丹 侯炜[1] GUI Yuerong;WANG Shuo;DONG Jun;ZHOU Tong;WANG Dandan;HOU Wei(Guang'anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China)

机构地区：[1]中国中医科学院广安门医院,北京100053

出　　处：《中国中医药信息杂志》2022年第12期30-37,共8页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：国家自然科学基金(82074239);北京市自然科学基金(7192181)。

摘　　要：目的运用网络药理学及分子对接技术,探讨益肾清肝方逆转乳腺癌内分泌治疗耐药的活性成分、潜在靶点和作用机制。方法通过TCMSP数据库筛选益肾清肝方的有效活性成分和作用靶点,利用GEO数据库检索获得乳腺癌内分泌治疗耐药的原始基因表达谱数据(GSE67916)以获取乳腺癌内分泌治疗耐药的相关靶基因,并与活性成分作用靶点相映射以得到共同靶点。通过STRING在线数据库构建益肾清肝方逆转乳腺癌内分泌治疗耐药PPI网络,并借助Cytoscape3.8.2软件筛选关键靶点;通过Metascape平台对关键靶点进行GO和KEGG富集分析,利用Cytoscape3.8.2软件构建靶点-活性成分-通路相互作用网络,对主要活性成分与关键靶点进行分子对接验证。结果共筛选出益肾清肝方活性成分122个,与疾病的交集靶点30个,主要涉及ESR1、TP53、STAT3、MAPK1、PGR等。KEGG富集分析显示FoxO、P53、雌激素、PI3K-Akt等信号通路可能是益肾清肝方逆转乳腺癌内分泌治疗耐药的关键信号通路,由靶点-活性成分-通路网络得出β-谷甾醇、木犀草素、山柰酚、槲皮素、苦参碱等是发挥作用的主要活性成分,分子对接显示主要活性成分与关键靶点对接活性良好。结论益肾清肝方中β-谷甾醇、木犀草素、山柰酚、槲皮素、苦参碱等可能通过抑制耐药相关蛋白表达、降低肿瘤干细胞自我更新能力,抑制耐药相关信号通路,发挥逆转乳腺癌对内分泌治疗耐药的作用。Objective To explore the active components,potential targets and mechanism of Yishen Qinggan Prescription in reversing the resistance of breast cancer endocrine therapy using network pharmacology and molecular docking technology.Methods Through the TCMSP database,the active components and potential targets of Yishen Qinggan Prescription were searched and screened.The original gene expression profiling data(GSE67916)of endocrine therapy resistance of breast cancer was retrieved from the GEO database to obtain the relevant target genes of endocrine therapy resistance of breast cancer,and mapped with the active components to obtain common targets.The protein-protein interaction network of intersection targets was constructed through the STRING online database,and the key targets were screened with the help of Cytoscape 3.8.2 software.GO and KEGG enrichment analysis of key targets was performed through the Metascape platform.The target-active components-pathway interaction network was constructed by Cytoscape 3.8.2 software.Molecular docking verification was performed on the main active components and key targets.Results A total of 122 active components of Yishen Qinggan Prescription were screened out,and 30 intersecting targets with diseases,mainly involving ESR1,TP53,STAT3,MAPK1,PGR,etc.KEGG enrichment analysis showed that FoxO,P53,Estrogen and PI3K-Akt signaling pathways may play an important role in the reversal of endocrine therapy resistance in breast cancer by Yishen Qinggan Prescription.According to the target-active ingredient-pathway interaction network,β-sitosterol,luteolin,kaempferol,quercetin,matrine,etc.were the main active components.Molecular docking showed that the main active components had good docking activity with key targets.Conclusion Active components such asβ-sitosterol,luteolin,kaempferol,quercetin,matrine and other active components in Yishen Qinggan Prescription may inhibit the expression of drug resistance-related proteins,reduce the self-renewal ability of cancer stem cells,and inhibit

关 键 词：网络药理学 分子对接 益肾清肝方 乳腺癌 抗雌激素治疗 耐药 作用机制 

分 类 号：R273.79[医药卫生—中西医结合] R285[医药卫生—中医肿瘤科]