Title:Exploring the Mechanism of Brucea Javanica against Ovarian Cancer based on Network Pharmacology and the Influence of Luteolin on the PI3K/AKT Pathway
Volume: 27
Issue: 1
Author(s): Jufan Zhu, Mengfei Han, Yiheng Yang, Renqian Feng, Yan Hu*Yuli Wang*
Affiliation:
- Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China
- Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China
Keywords:
Brucea Javanica, luteolin, ovarian cancer, core targets, network pharmacology, molecular docking, PI3K, AKT.
Abstract: Background: 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.
Objective: 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.
Methods: 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.
Results: 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.
Conclusion: It was verified in vitro that luteolin could hinder OC cell proliferation and activate the
PI3K/AKT pathway to lead to apoptosis.