基于网络药理学分子对接探讨山慈菇抗三阴性乳腺癌的分子机制  

Exploring the Molecular Mechanism of Cremastra appendiculata Anti-triple Negative Breast Cancer Based on the Network Pharmacology and Molecular Docking

作　　者：杨冬冬 刘颖 曹晓东[2] 张楠[3] 张子英 马丽杰 YANG Dongdong;LIUYing;CAO Xiaodong;ZHANG Nan;ZHANG Ziying;MA Lijie(Basic Medical College of Inner Mongolia Medical University,Hohhot 010110,china;The Center for New Drug Safety Evaluation and Research of Inner Mongolia Medical University,Hohhot 010110,china;Public Health of Inner Mongolia Medical University,Hohhot 010110,china)

机构地区：[1]内蒙古医科大学基础医学院,内蒙古呼和浩特010110 [2]内蒙古医科大学新药安全评价研究中心,内蒙古呼和浩特010110 [3]内蒙古医科大学慢性病分子流行病实验室,内蒙古呼和浩特010110

出　　处：《特产研究》2023年第1期64-71,81,共9页Special Wild Economic Animal and Plant Research

基　　金：内蒙古自治区自然科学基金项目(2020MS08136、2020BS08015、2020LH08041和2020LH08036)。

摘　　要：本研究基于网络药理学与分子对接的方法探讨山慈菇治疗三阴性乳腺癌的作用机制。利用TCMSP数据库和文献中获得山慈菇化学成分,在Swiss Target Prediction平台上搜索活性成分靶点;采用OMIM、GeneCards数据库检索三阴性乳腺癌靶点,并通过String构建蛋白质互作网络,使用DAVID数据库对核心靶点进行GO分析和KEGG通路富集分析;另外选取部分化合物和靶点使用Autodock软件进行分子对接验证;运用Western blot法检测相关调控靶点蛋白的表达。结果显示,共筛选出12个山慈菇活性成分,97个关键靶点,分子对接发现主要靶点HSP90AA1、EGFR、MAPK1、JUN和PIK3CA均与活性成分对接较好。山慈菇的作用靶点富集于PI3K-AKT信号通路,山慈菇通过降低p-AKT和p-PI3K的表达水平进行调控乳腺癌细胞的增殖、凋亡和迁移。本研究初步预测了山慈菇的有效活性成分、关键靶点和作用机制,可为山慈菇治疗三阴性乳腺癌的临床应用提供依据。To explore the molecular mechanisms of Cremastra appendiculata against triple-negative breast cancer based on the network pharmacology and molecular docking. TCMSP and literature was used to collect the active compounds of Cremastra appendiculata. The disease targets related to triple-negative breast cancer were obtained from the OMIM and GeneCards online databases. String database were used to construct the PPI network. Gene ontology(GO)analysis and KEGG metabolic pathways of the key targets were analyzed using the DAVID database. The molecular docking verification of active components and core targets was conductecd with Autodock software. Finally, the expression of related regulatory proteins was detected by Western blot. The results showed that 12 active components of Cremastra appendiculata were retrieved, and the medicinal and the disease shared 97 targets, The molecular-docking results further showed the core targets including HSP90AA1、EGFR、MAPK1 had a good binding effect. The targets of Cremastra appendiculata are enriched in the PI3KAKT signaling pathway, and it can regulates the proliferation, apoptosis and migration of breast cancer cells by reducing the expression levels of p-AKT and p-PI3K. The result of the study preliminarily predicts the effective active ingredients, key targets and mechanism of Cremastra appendiculata, which would provide a basis for the clinical application of Cremastra appendiculata in the treatment of triple-negative breast cancer.

关 键 词：山慈菇 三阴性乳腺癌 网络药理学 分子对接 

分 类 号：R285[医药卫生—中药学]