Exploring the therapeutic potential and in vitro validation of baicalin for the treatment of triple-negative breast cancer

ObjectiveTo explore the mechanism of action of baicalin (BA) in the treatment of triple-negative breast cancer (TNBC) based on network pharmacology, molecular docking and molecular dynamics simulations and in vitro validation.MethodsThe inhibitory effects of different concentrations of baicalin on t...

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Main Authors: Yuan Ma, Ying Pan, Qiancheng Zhao, Chongheng Zhang, Haitao He, Lihua Pan, Jianling Jia, Aiping Shi, Yiming Yang, Wenfeng Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1530056/full
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author Yuan Ma
Ying Pan
Qiancheng Zhao
Chongheng Zhang
Haitao He
Lihua Pan
Jianling Jia
Aiping Shi
Yiming Yang
Wenfeng Zhang
author_facet Yuan Ma
Ying Pan
Qiancheng Zhao
Chongheng Zhang
Haitao He
Lihua Pan
Jianling Jia
Aiping Shi
Yiming Yang
Wenfeng Zhang
author_sort Yuan Ma
collection DOAJ
description ObjectiveTo explore the mechanism of action of baicalin (BA) in the treatment of triple-negative breast cancer (TNBC) based on network pharmacology, molecular docking and molecular dynamics simulations and in vitro validation.MethodsThe inhibitory effects of different concentrations of baicalin on the proliferation of MDA-MB-231, 4T1, MCF-7, and MCF-10A cell lines were evaluated by CCK8 assay with clone formation assay. Three compound target prediction platforms, Swiss Target Prediction, SEA and Pharmmapper, were used to predict baicalin-related targets, and mapped with the triple-negative breast cancer-related targets retrieved from GeneCards and OMMI databases to obtain the potential targets of baicalin for the treatment of triple-negative breast cancer; the STRING database and the STRING database and Cytoscape software were used to construct the protein interaction network and screen the core targets; GO and KEGG enrichment analyses were performed on the core targets; the binding of baicalin to the key targets of triple-negative breast cancer was verified by molecular docking and molecular dynamics simulation; and the expression of the relevant proteins was verified.ResultsBaicalin showed more obvious antiproliferative effects on triple-negative breast cancer cell lines at certain concentrations, and had less effect on the proliferation of normal breast cells. A total of nine core targets of baicalin in the treatment of triple-negative breast cancer, including AKT1, ESR1, TNF-α, SRC, EGFR, MMP9, JAK2, PPARG, and GSK3B, were identified through the construction of the PPI protein interactions network and the ‘Traditional Chinese Medicine-Component-Target-Disease’ network, and a total of 252 targets related to the intersected targets were identified in the GO analysis. GO analysis enriched a total of 2,526 Biological process, 105 Cellular component and 250 Molecular function related to the intersecting targets; KEGG analysis enriched a total of 128 signaling pathways related to the intersecting targets; molecular docking results and molecular dynamics studies found that baicalin was able to interact with MMP9, TNF-α, JAK2, PPARG, GSK3B, and other core targets of baicalin for the treatment of triple-negative breast, MMP9, TNF-α, and JAK2 target proteins, and had significant changes in the expression levels of the target proteins.ConclusionBaicalin inhibits the protein expression of MMP9, TNF-α and JAK2 and their related signaling pathways in the treatment of triple-negative breast cancer.
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spelling doaj-art-4bf723c2fc7246b0a6f8659732f2e83a2025-08-20T02:29:46ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-04-011610.3389/fphar.2025.15300561530056Exploring the therapeutic potential and in vitro validation of baicalin for the treatment of triple-negative breast cancerYuan Ma0Ying Pan1Qiancheng Zhao2Chongheng Zhang3Haitao He4Lihua Pan5Jianling Jia6Aiping Shi7Yiming Yang8Wenfeng Zhang9School of Basic Medicine, Changchun University of Traditional Chinese Medicine, Changchun, Jilin, ChinaDepartment of Histology and Embryology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, ChinaDepartment of Cell Biology and Medical Genetics, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, ChinaSchool of Basic Medicine, Changchun University of Traditional Chinese Medicine, Changchun, Jilin, ChinaDepartment of Cell Biology and Medical Genetics, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, ChinaCollege of Basic Medical Sciences, Jilin University, Changchun, Jilin, ChinaDepartment of Breast Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, ChinaDepartment of Breast Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, ChinaDepartment of Cell Biology and Medical Genetics, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, ChinaSchool of Basic Medicine, Changchun University of Traditional Chinese Medicine, Changchun, Jilin, ChinaObjectiveTo explore the mechanism of action of baicalin (BA) in the treatment of triple-negative breast cancer (TNBC) based on network pharmacology, molecular docking and molecular dynamics simulations and in vitro validation.MethodsThe inhibitory effects of different concentrations of baicalin on the proliferation of MDA-MB-231, 4T1, MCF-7, and MCF-10A cell lines were evaluated by CCK8 assay with clone formation assay. Three compound target prediction platforms, Swiss Target Prediction, SEA and Pharmmapper, were used to predict baicalin-related targets, and mapped with the triple-negative breast cancer-related targets retrieved from GeneCards and OMMI databases to obtain the potential targets of baicalin for the treatment of triple-negative breast cancer; the STRING database and the STRING database and Cytoscape software were used to construct the protein interaction network and screen the core targets; GO and KEGG enrichment analyses were performed on the core targets; the binding of baicalin to the key targets of triple-negative breast cancer was verified by molecular docking and molecular dynamics simulation; and the expression of the relevant proteins was verified.ResultsBaicalin showed more obvious antiproliferative effects on triple-negative breast cancer cell lines at certain concentrations, and had less effect on the proliferation of normal breast cells. A total of nine core targets of baicalin in the treatment of triple-negative breast cancer, including AKT1, ESR1, TNF-α, SRC, EGFR, MMP9, JAK2, PPARG, and GSK3B, were identified through the construction of the PPI protein interactions network and the ‘Traditional Chinese Medicine-Component-Target-Disease’ network, and a total of 252 targets related to the intersected targets were identified in the GO analysis. GO analysis enriched a total of 2,526 Biological process, 105 Cellular component and 250 Molecular function related to the intersecting targets; KEGG analysis enriched a total of 128 signaling pathways related to the intersecting targets; molecular docking results and molecular dynamics studies found that baicalin was able to interact with MMP9, TNF-α, JAK2, PPARG, GSK3B, and other core targets of baicalin for the treatment of triple-negative breast, MMP9, TNF-α, and JAK2 target proteins, and had significant changes in the expression levels of the target proteins.ConclusionBaicalin inhibits the protein expression of MMP9, TNF-α and JAK2 and their related signaling pathways in the treatment of triple-negative breast cancer.https://www.frontiersin.org/articles/10.3389/fphar.2025.1530056/fullbaicalintriple-negative breast cancermolecular dynamics simulationmolecular dockingnetwork pharmacology
spellingShingle Yuan Ma
Ying Pan
Qiancheng Zhao
Chongheng Zhang
Haitao He
Lihua Pan
Jianling Jia
Aiping Shi
Yiming Yang
Wenfeng Zhang
Exploring the therapeutic potential and in vitro validation of baicalin for the treatment of triple-negative breast cancer
Frontiers in Pharmacology
baicalin
triple-negative breast cancer
molecular dynamics simulation
molecular docking
network pharmacology
title Exploring the therapeutic potential and in vitro validation of baicalin for the treatment of triple-negative breast cancer
title_full Exploring the therapeutic potential and in vitro validation of baicalin for the treatment of triple-negative breast cancer
title_fullStr Exploring the therapeutic potential and in vitro validation of baicalin for the treatment of triple-negative breast cancer
title_full_unstemmed Exploring the therapeutic potential and in vitro validation of baicalin for the treatment of triple-negative breast cancer
title_short Exploring the therapeutic potential and in vitro validation of baicalin for the treatment of triple-negative breast cancer
title_sort exploring the therapeutic potential and in vitro validation of baicalin for the treatment of triple negative breast cancer
topic baicalin
triple-negative breast cancer
molecular dynamics simulation
molecular docking
network pharmacology
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1530056/full
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