Exploring the Mechanism of Brucea Javanica against Ovarian Cancer based on Network Pharmacology and the Influence of Luteolin on the PI3K/AKT Pathway.

Abstract

Ovarian cancer (OC) is a commonly diagnosed female cancer around the world. The Chinese herbal medicine Brucea Javanica has an anti-cancer effect. However, there is no relevant report on whether Brucea Javanica is effective in treating OC, and the corresponding mechanism is also unknown. This study was projected to excavate the active components and underpinned molecular mechanisms of Brucea Javanica in treating ovarian cancer (OC) through network pharmacology combined with in vitro experiments. The essential active components of Brucea Javanica were selected using the TCMSP database. The OC-related targets were selected by GeneCards, intersecting targets were obtained by Venn Diagram. The core targets were obtained through the PPI network and Cytoscape, and the key pathway was gained through GO and KEGG enrichment analyses. Meanwhile, docking conformation was observed as reflected by molecular docking. MTT, colony formation assay and flow cytometer (FCM) analysis were performed to determine cell proliferation and apoptosis, respectively. Finally, Levels of various signaling proteins were evaluated by western blotting. Luteolin, β-sitosterol and their corresponding targets were selected as the essential active components of Brucea Javanica. 76 intersecting targets were obtained by Venn Diagram. TP53, AKT1, and TNF were obtained through the PPI network and Cytoscape, and the key pathway PI3K/AKT was gained through GO and KEGG enrichment analyses. A good docking conformation was observed between luteolin and AKT1. Luteolin could hinder A2780 cell proliferation, induce cell apoptosis and enhance the inhibition of the PI3K/AKT pathway. It was verified in vitro that luteolin could hinder OC cell proliferation and activate the PI3K/AKT pathway to lead to apoptosis.