Title:Mechanism of the Effect of Scopolamine on Breast Cancer: Determination by Network Pharmacology and Bioinformatics
Volume: 20
Author(s): Yang Xiao, Qiang Guo, Yichen Li, Mengcong Ma, Yu Sun, Qing Gu and Yunfeng Xiao*
Affiliation:
- Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
Keywords:
Bioinformatics, breast cancer, network pharmacology, scopolamine.
Abstract: Background: To a certain extent, traditional Chinese medicine (TCM)-based anesthesia
has replaced opiate administration in recent years. Preliminary drug screening has revealed
that scopolamine may affect breast cancer (BC) metastasis by an unknown mechanism.
Methods: Network pharmacology, bioinformatics, and protein-protein interaction (PPI) topological
analysis were implemented to identify the core genes linking scopolamine and BC. The core
genes were then subjected to gene expression profiling interactive analysis (GEPIA). The top
ten pathways were detected by gene ontology (GO) enrichment and Kyoto Encyclopedia of
Genes and Genomes (KEGG) pathway analyses. The impact of immune infiltration on the core
gene difference and survival analyses was then determined. Molecular docking was then performed
on the core genes and the main active components.
Results: Protein kinase 1 (AKT1), epidermal growth factor receptor (EGFR), heat shock protein
90 alpha class A (HSP90AA1), caspase 3 (CASP3), and estrogen receptor 1 (ESR1) were the
key genes in the interaction between scopolamine and BC cells. The KEGG enrichment analysis
disclosed that the top ten pathways significantly associated with the scopolamine response in
BC included "protein glycosylation," "phosphoinositide 3-kinase (PI3K)-Akt signaling," "mitogen-
activated protein kinase (MAPK) signaling" and others. The AKT1, EGFR, and especially
the HSP90AA1 expression levels were correlated with survival in patients with BC. Immune
infiltration also influenced the survival outcome. Molecular docking demonstrated that scopolamine
bound and formed stable complexes with the protein products of all five aforementioned
genes.
Conclusion: Scopolamine has multiple targets regulating BC cell function and may increase the
risk of metastasis during treatment. Therefore, it should be preoperatively administered with
caution to patients with BC.
