Exploring the Potential of Chaihu-Danggui Tang in Breast Cancer Treatment Based on Network Pharmacology, Molecular Docking, and Experimental Validation.

Background: Chaihu-Danggui Tang (CHDGT) has a long history in traditional Chinese medicine (TCM) as an adjuvant therapy for breast cancer (BC), but its precise anti-tumor mechanisms remain unknown. In this study, we used network pharmacology, molecular docking, and experimental validation methods to investigate the core components, key targets, and possible mechanisms through which CHDGT may exert therapeutic effects in BC treatment.

Methods: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) was employed to obtain the active ingredient and targets of CHDGT. Meanwhile, the GeneCards databases were used to retrieve pertinent targets for BC. The Venn plot was used to obtain intersection targets. Cytoscape software was used to construct an "CHDGT-active ingredients-targets" network and identify core targets. The common targets after STRING processing were imported into the Metascape database for GO and KEGG pathway enrichment analysis. Molecular docking of key ingredients and core targets of drugs was accomplished using Autodock and PyMol software. The cell and animal experiments confirmed CHDGT efficacy and mechanism in treating BC.

Results: We screened 5 key effector components, 8 core targets, and multiple signaling pathways of CHDGT in treating BC. In vitro, the results of CCK-8 assay showed that CHDGT can dose-dependently inhibits BC cell growth, and at 100 mg L^-1 after 48 hours, the cell inhibition rate reached approximately 50%. Further analysis showed that CHDGT can promote apoptosis of BC cell, and regulate the expression levels of apoptosis-related genes, such as Caspase3, p53, and Bcl-2. The animal experiments verified that CHDGT can significantly inhibit the progression of BC, the tumor inhibition rate of CHDGT-H groups was as high as 60.06 ± 4.82%. In addition, H&E staining and blood biochemical analysis suggest that CHDGT exhibits favorable safety.

Conclusion: This study may provide perspectives for the development of anticancer Chinese herbs for the treatment of BC.