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Updated: Jun 16, 2026
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Multi-omics integration and experimental validation reveal the mechanism of berberine against triple-negative breast
Ying Zhang1,2,3, Tao Lu1,2,3, Kaixuan Liu1,2
1Department of Pathology, Guizhou Medical University, Guiyang, China.
Introduction:
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer lacking effective therapeutic options. Berberine (BBR), a natural isoquinoline alkaloid, has shown anti-tumor potential, but its systemic mechanism of action in TNBC has not been fully elucidated.
Methods:
This study adopted an integrated strategy combining network pharmacology, transcriptomic analysis, molecular docking, molecular dynamics simulation, and multi-level in vitro experimental validation. Targets of BBR were predicted through multiple databases, TNBC-related genes were screened by integrating GEO and TCGA data, key targets and tumor microenvironment characteristics were analyzed using WGCNA, PPI networks, and single-cell sequencing data, and the biological effects of BBR were validated through molecular docking, dynamics simulation, and cellular experiments.
Results:
A total of 182 common targets of BBR and TNBC were identified, with 12 genes, including SRC, STAT3, and EGFR, being identified as hub targets. Immune infiltration analysis indicated that BBR targets were associated with the tumor immune microenvironment. Single-cell sequencing showed that these targets are primarily enriched in tumor cells and macrophages, and molecular docking and dynamics simulations revealed that BBR has high affinity with SRC (-8.8 kcal/mol). In vitro experiments confirmed that BBR can concentration-dependently inhibit TNBC cell proliferation, induce apoptosis, increase ROS levels, and significantly reduce the proportion of CD133+ stem cells and tumor sphere formation capacity. Western blot analysis showed that BBR downregulated the activity of the p-PI3K/p-AKT and p-SRC/p-STAT3 pathways.
Conclusion:
BBR inhibits TNBC cell proliferation, induces apoptosis, weakens tumor stemness, and may regulate the tumor immune microenvironment through multi-target, multi-pathway synergistic effects. This study systematically reveals the integrative mechanism of BBR against TNBC, providing a theoretical basis for its development as a multi-target natural anti-tumor drug.
Insights
Berberine (BBR) effectively inhibits triple-negative breast cancer (TNBC) by targeting multiple pathways, reducing cell proliferation, and enhancing apoptosis. This natural compound shows promise as a multi-target anti-cancer drug.
Area of Science:
- Integrative oncology
- Natural product pharmacology
- Computational biology
Background:
- Triple-negative breast cancer (TNBC) is an aggressive cancer subtype with limited therapeutic options.
- Berberine (BBR), a natural alkaloid, exhibits anti-tumor properties, but its precise mechanism in TNBC requires elucidation.
Purpose of the Study:
- To systematically investigate the multi-target mechanism of Berberine (BBR) against triple-negative breast cancer (TNBC).
- To explore the potential of BBR as a natural therapeutic agent for TNBC.
Main Methods:
- Integrated approach combining network pharmacology, transcriptomic analysis, molecular docking, molecular dynamics, and in vitro validation.
- Screening of BBR targets and TNBC-related genes using multiple databases (GEO, TCGA).
- Analysis of key targets and tumor microenvironment using WGCNA, PPI networks, and single-cell sequencing.
Main Results:
- Identified 182 common targets, with SRC, STAT3, and EGFR as key hub targets.
- BBR demonstrated high affinity with SRC and modulated PI3K/AKT and SRC/STAT3 pathways.
- In vitro studies confirmed BBR inhibits TNBC proliferation, induces apoptosis, reduces stemness, and impacts the tumor immune microenvironment.
Conclusions:
- Berberine exerts anti-TNBC effects through multi-target, multi-pathway synergistic actions, including inhibiting proliferation and inducing apoptosis.
- BBR shows potential in regulating the tumor immune microenvironment and weakening tumor stemness.
- This study provides a mechanistic basis for developing BBR as a natural multi-target anti-cancer drug for TNBC.
