Mechanistic Study of the Herbal Drug FDY003 for the Treatment of HER2-Positive Breast Cancer via Network Pharmacology Analysis

Abstract

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer (HER2PBC), a subset of breast cancer (BC), results from overexpression and hyperactivation of the oncogene HER2. This subtype is observed in 20-30% of all patients with BC. FDY003 is an herbal prescription comprising Lonicera japonica Thunberg, Artemisia capillaris Thunberg, and Cordyceps militaris, and its suppressive effects on HER2PBC cells have been previously investigated. However, its anticancer mechanisms, and specifically its actions on HER2PBC cells, have not been fully elucidated. Thus, we applied network pharmacology (NP) methodology to FDY003, a widely used technique that effectively and comprehensively investigates the pharmacological features of herbal drugs, to explore its mechanisms against HER2PBC. FDY003 exhibited inhibitory activity on HER2PBC cell viability, and it improved the efficacy of the HER2-targeting therapeutic. NP analysis identified 8 bioactive ingredients and 69 HER2PBC-associated genes that were targeted by those ingredients. Gene ontology analysis of the HER2PBC-associated genes targeted by FDY003 indicated that FDY003 might exhibit pharmacological effects by regulating the behaviors of HER2PBC cells, such as proliferation/growth arrest and survival/death. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that FDY003 might affect critical pathways responsible for HER2PBC pathology, including the ErbB, HIF-1, JAK-STAT, MAPK, p53, PD-L1/PD-1, PI3K-Akt, Ras, TNF, and VEGF cascades. The NP analysis results suggested multitarget-multipathway regulatory characteristics of FDY003 against HER2PBC, focusing on its network mechanisms.