Mechanisms of Honeysuckle Against Triple-negative Breast Cancer Based on Network Pharmacology and Molecular Docking

Abstract

[Objective] To study the mechanism of action of the Honeysuckle against triple-negative breast cancer based on network pharmacology and molecular docking method, to provide a reference for elucidating its clinical anti-breast cancer mechanism. [Methods] The Honeysuckle active ingredients and their targets were screened by TCMSP and SwissTargetPrediction databases, and the target genes related to breast cancer were collected by GeneCards, OMIM and Disgenet databases, and the "Drug-Active Ingredient-Target-Disease" was constructed by using Cytoscape 3.9.1 software. The Cytoscape 3.9.1 software was used to construct a "drug-active ingredient-target-disease" network. The potential targets were imported into the STRING database to build a protein-protein interactions network (PPI). The core targets were annotated with the GO function and analyzed by KEGG pathway enrichment through the DAVID database. Molecular docking was carried out between the main active ingredients of the Honeysuckle and the potential targets through the Pymol software and AutoDock software. Molecular docking was performed using Pymol and AutoDock software. [A total of 23 active ingredients and 591 targets of the Honeysuckle, 1,811 triple-negative breast cancer disease targets, 186 potential targets, and 38 genes in the PPI network were screened in the two-component target databases, TCMSP and SwissTargetPrediction, and the three disease databases, GeneCards, OMIM, and Disgenet. In the PPI network, 38 key targets of the honeysuckle for breast cancer treatment were obtained, and after GO and KEGG analysis, 1,118 GO analysis results and 157 KEGG pathways were obtained. The GO analysis results showed that the honeysuckle's anti-breast cancer may be related to the transcription initiation process of the RNA polymerase II promoter, nuclear chromatin, DNA binding, etc.; the KEGG analysis results showed that the honeysuckle may be involved in the cancer pathway and the anti-breast cancer may involve the cancer pathway. The results of the KEGG analysis indicated that the honeysuckle anti-breast cancer might be involved in the cancer pathway, proteoglycan signaling pathway, microRNA pathway, thyroid hormone signaling pathway, etc. The molecular docking results showed that the predicted key components, quercetin and lignocerol, had better binding properties to the core targets, EP000, ERBB2, GAPDH, and MAPK3. [Conclusion] The anti-triple-negative breast cancer of the Honeysuckle mainly involves EP000, ERBB2, GAPDH , MAPK3 and 157 signaling pathways, and its active ingredients can inhibit the growth of tumor cells through multi-targets, multi-pathways, and multi-mechanisms.