基于网络药理学探讨化瘀丸辅助免疫检查点抑制剂治疗三阴性乳腺癌作用机制  

Exploring mechanism of Huayu Pills combined with immunocheckpoint inhibitors in treating triple-negative breast cancer based on network pharmacology

作　　者：杨雯靖 杨国旺[1] Yang Wenjing;Yang Guowang(Department of Oncology,Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,Beijing 100010,China)

机构地区：[1]首都医科大学附属北京中医医院肿瘤科,北京100010

出　　处：《国际中医中药杂志》2024年第2期203-208,共6页International Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(82205219、82174453);北京市医院管理中心青年人才培养“青苗”计划(QML20231004)。

摘　　要：目的运用网络药理学方法探讨化瘀丸辅助免疫检查点抑制剂治疗三阴性乳腺癌(TNBC)的潜在作用机制。方法利用TCMSP、PubChem、STITCH和SwissTargetPrediction数据库分析化瘀丸潜在作用靶点。基于癌症和肿瘤基因图谱(TCGA)数据库筛选TNBC疾病靶点。将药物-疾病映射靶点进行PPI网络构建、关键靶点筛选和模块分析, 并运用DAVID数据库进行GO功能注释和KEGG信号通路富集分析。大鼠灌胃化瘀丸水煎液3.94 g/kg, 连续给药4 d, 制备含药血清。将人脐静脉血管内皮细胞(HUVEC)按随机数字表法分为对照组和实验组, 实验组给予化瘀丸含药血清干预24 h后, 接种于Matrigel已凝固的48孔板中, 3 h后观察HUVEC血管形成情况。结果获得化瘀丸治疗TNBC的可能作用靶点130个, VEGFA为核心作用靶点, 血管生成、缺氧、凝血级联反应可能为化瘀丸治疗TNBC的主要相关功能及关键信号通路。体外研究表明, 化瘀丸含药血清可促进HUVEC细胞肿瘤血管正常化。结论化瘀丸可能通过VEGF靶点促进肿瘤血管正常化(血管生成、缺氧、凝血级联反应), 可辅助免疫检查点抑制剂发挥治疗TNBC的功效。Objective To explore the potential mechanism of Huayu Pills in the treatment of TNBC(triple-negative breast cancer)using network pharmacology.Methods TCMSP(Traditional Chinese Medicine Systems Pharmacology),PubChem,STITCH and SwissTargetPrediction databases were used to analyze the potential targets of Huayu Pills.TNBC disease targets were screened based on the TCGA(The Cancer Genome Atlas)database.The drug-disease mapping target was constructed by PPI network,key target screening and module analysis,and the DAVID database was used for GO function annotation and KEGG signal pathway enrichment analysis.SD rats were orally administered 3.94 g/kg of Huayu Pills decoction for 4 days to prepare medicated serum.HUVEC cells were randomly divided into a control group and an experimental group using a random number table method.The experimental group received intervention with Huayu Pills containing serum for 24 hours,inoculated in matrigel's solidified 48 well plate and HUVEC angiogenesis was observed 3 hours later.Results 130 possible targets of Huayu Pills in the treatment of TNBC were obtained.VEGFA is the core target.The cascade of angiogenesis,hypoxia,and blood coagulation may be the main functions and key signals of Huayu Pills in the treatment of TNBC.In vitro studies have shown that serum containing Huayu Pills can promote the normalization of tumor blood vessels in HUVEC cells.Conclusion Huayu Pills may promote tumor vascular normalization(angiogenesis,hypoxia,coagulation cascade reactions)through VEGF targets,and can assist immune checkpoint inhibitors in the treatment of TNBC.

关 键 词：三阴性乳腺肿瘤 网络药理学 化瘀丸 药理作用分子作用机制(中药) 

分 类 号：R737.9[医药卫生—肿瘤]