Molecular targets of vortioxetine mediating glioblastoma suppression revealed by gene and protein network analyses and molecular docking simulations

作者：Chuanjun Zhuo, Chao Li, Qiuyu Zhang, Lei Yang, Ying Zhang, Ximing Chen, Xiaoyan Ma, Ranli Li, Lina Wang, Hongjun Tian · 发表于：The International Journal of Neuropsychopharmacology · 年份：2025 · DOI：10.1093/ijnp/pyaf029 · 被引用次数：6 · 研究领域：Cancer, Stress, Anesthesia, and Immune Response、Treatment of Major Depression、Glioma Diagnosis and Treatment

BACKGROUND: Vortioxetine is a serotonin reuptake inhibitor and serotonin receptor modulator used for the treatment of major depressive disorder, but recent studies have also reported anticancer effects in models of glioblastoma. Given the well-established benefits of drug repositioning, we examined the pharmacological mechanism for these anticancer actions using bioinformatics and molecular docking. METHODS: Putative molecular targets for vortioxetine were identified by searching DrugBank, GeneCards, SwissTargetPrediction, Comparative Toxicogenomics Database, and SuperPred databases, while glioblastoma-related proteins were identified using GeneCards, Online Mendelian Inheritance in Man; , and Therapeutic Target Database . A protein-protein interaction (PPI) network was constructed from vortioxetine targets also involved in glioblastoma to identify core (hub) targets, which were then characterized by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses using database for annotation, visualization, and integrated discovery. Cytoscape was utilized to generate a drug-pathway-target-disease network, and molecular docking simulations were performed to evaluate direct interactions between vortioxetine and core target proteins. RESULTS: A total of 234 unique vortioxetine protein targets were identified. Among 234 vortioxetine targets identified, 48 were also related to glioblastoma. Topological analysis of the PPI network revealed 5 core ...