The Pharmacological Mechanisms of Xiaochaihutang in Treating Breast Cancer Based on Network Pharmacology.

Background: As a classic prescription in Chinese medicine treatment, Xiaochaihutang (XCHT) can improve the clinical effect and reduce serum tumor markers in patients with breast cancer (BC). However, there has not been any study to confirm the mechanism. We used bioinformatics analysis and network pharmacology to find the potential targets. Methods: The differentially expressed genes (DEGs) of BC were identified from the Cancer Genome Atlas (TCGA) dataset. Then, we utilized weighted coexpression network analysis (WGCNA) with the same dataset. The target genes of BC were obtained by comparing genes of DEGs and in significant modules of WGCNA. Drug targets of XCHT from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database were intersected with the targets of BC. The protein-protein interaction (PPI) of the drug targets was analysed by using the STRING database. We utilized the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analysis (KEGG) enrichment analysis to identify the specific pathways and key target proteins. Receiver operator characteristic (ROC) curve was used as the verification of drug targets. Molecular docking was performed to visualize the patterns of interactions between the effective molecule and targeted protein. Results: We obtained a set of 21 target genes, which mainly encode neurotransmitter receptors or related transporters, such as OPRD1, 5-HT2A, and so on. In addition, enrichment analyses of 21 target genes showed that they were mainly concentrated in pathways related to the nervous system. Molecular docking was performed on the target gene of BC. Six active compounds can enter the active pocket of target gene, namely, naringenin, beta-sitosterol, coumestrol, nuciferine, beta-sitosterol, and protopine, thereby exerting potential therapeutic effects in BC. Conclusions: Our analysis shows that the mechanism of XCHT in the treatment of BC is mainly acting on the neurogenesis in the microenvironment of breast tumor tissue.