Network Toxicology Combined with Molecular Docking was Used to Study the Multi-Target Regulation and Toxicity Mechanism of Sorafenib on Hepatocellular Carcinoma
TANG Ming
SUN Li'e
Abstract：Objective This study aims to promote network toxicology and molecular docking strategies to effectively evaluate the multi-target regulation and toxicity mechanism of sorafenib in hepatocellular carcinoma(HCC).Methods Firstly,obtained a preliminary overview of the toxicity of sorafenib using the ProTox-Ⅱ and ADMETlab 2.0 databases.Subsequently,177 potential targets related to sorafenib and hepatocellular carcinoma were identified by using the SwissTargetPrediction,CTD,GeneCards,OMIM and TTD databases.Cytoscape 3.10.3 network topology analysis screened the core targets,then conducted gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathway analyses on the core targets,and finally performed rapid molecular docking using CB-Dock2.Results The core targets of sorafenib include tumor suppressor protein(TP53),catenin β1(CTNNB1),protein kinase B1(AKT1),signal transduction and activator of transcription 3(STAT3),epidermal growth factor(EGFR),B-cell lymphoma-2(BCL2),CASP3,and proto-oncogene(MYC)),transcription factor AP-1 subunit(JUN),tumor necrosis factor(TNF).Analysis of the GO and KEGG pathways indicated that the core target of sorafenib in hepatocellular carcinoma was mainly enriched in the PI3K-Ak signaling pathway.Rapid molecular docking was carried out using CB-Dock2,confirming the interaction between sorafenib and five core target proteins(CTNNB1,AKT1,TP53,STAT3 and EGFR).Conclusion Sorafenib has a strong binding ability with each core target,further proving that these targets are the core targets of sorafenib in the treatment of hepatocellular carcinoma.This provides a theoretical basis for sorafenib in the treatment of hepatocellular carcinoma.
Keywords：Network toxicologyMolecular dockingSorafenibHepatocellular carcinoma
Publication Date：2025-08-15
Online Publishing Date：2025-11-17(First online date of this platform, not the publication date of the document)
Pages：6( 5-9,后插2-后插3 )