DefinePK

Abstract

Background and Objective: Glioblastoma (GBM) is one of the deadliest cancers. However, due to the unclear pathogenesis of GBM, many drugs cannot be effective. Therefore, it is of great significance to develop new safe and effective therapeutic drugs and explore the regulatory mechanism of GBM. Brucine can inhibit tumor proliferation, but the mechanism of brucine on GBM has not been scientifically explained at the cellular and molecular levels. In this study, the inhibitory mechanism of Brucine on GBM was explored and verified by experiments. Materials and Methods: The common targets of Brucine and GBM are determined by constructing the Venn diagram of intersecting targets. Common targets were visualized through String databases and protein interaction networks (PPI) were constructed. The Hub genes were screened using Cytoscape 3.9.1 and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed using DAVID online database. The inhibitory effect of Brucine on GBM U251 cells was observed in vitro. Results: Brucine and GBM had 40 intersection targets and the top 5 clustering networks were selected as the Hub targets, successively EGFR, AKT1, MTOR, HSP90AA1 and JUN. The targets mainly involve focal adhesion, cancer-related pathways, the main signaling pathways PI3K-Akt signaling pathway and VEGF signaling pathway. Brucine inhibited the proliferation of GBMU251 cells in a time- and dose-dependent manner. Conclusion: Brucine showed multi-target and multi-pathway inhibition on GBM and played an active pharmacological role in in vitro experiments, which can provide references for studying the mechanism of Brucine in GBM.