Study on the Mechanism of Tetrastigma hemsleyanum against Hepatocellular Carcinoma Based on Network Pharmacology,Molecular Docking and Experimental Verification
10.19879/j.cnki.1005-5304.202404227
- VernacularTitle:基于网络药理学、分子对接和实验验证的三叶青治疗肝细胞癌作用机制研究
- Author:
Yifei GU
1
;
Zijin XU
;
Ping WANG
Author Information
1. 无锡市中医医院药学部,江苏 无锡 214000
- Keywords:
Tetrastigma hemsleyanum;
hepatocellular carcinoma;
network pharmacology;
molecular docking;
MAPK;
AP-1
- From:
Chinese Journal of Information on Traditional Chinese Medicine
2024;31(11):51-59
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the mechanism of Tetrastigma hemsleyanum(TH)in the treatment of hepatocellular carcinoma(HCC)through network pharmacology;To conduct experimental verification.Methods The active components and targets of TH were screened from CNKI,Wanfang Data,VIP,PubMed,Web of Science and TCMSP databases.OncoDB.HCC,GeneCards,OMIM and DrugBank databases were searched to collect HCC-related targets,and Cytoscape software was used to construct drug-active components-target-disease network.Protein-protein interaction(PPI)was analyzed using STRING database.The GO and KEGG pathway enrichment were analyzed using the Metascape database.AutoDock were used for molecular docking of key targets and their corresponding components.MTT colorimetric assay and cell morphology observation were used to detect the proliferation of human liver cancer HepG2 cells.Cell migration and invasion were observed through cell scratch experiment and Transwell chamber experiment.Annexin Ⅴ/PI double staining and flow cytometry were used to detect cell apoptosis,while RT-PCR and Western blot were used to detect related protein expression.Results The network pharmacological analysis showed that there were 16 active components in TH,228 action targets,and 157 targets related to HCC.JUN,AKT1,MAPK1 and TP53 would be the core targets of TH for the treatment of HCC.The core pathways were IL-17 signaling pathway,TNF signaling pathway,P53 signaling pathway,and PI3K-Akt signaling pathway,which were closely related to HCC.The molecular docking results showed that there was a good binding effect between the main active components and the core target of TH.The cell experiment results showed that each dose group of TH could significantly inhibit the proliferation,migration,and invasion of HepG2 cells,promote apoptosis,down-regulate the expressions of AP-1 and MAPK1,and up-regulate the expression of TP53.Conclusion TH can inhibit the proliferation,migration and invasion of HepG2 cells and promote their apoptosis.The mechanism may be related to the down-regulation of AP-1,MAPK1 protein expression and up-regulation of TP53 protein expression.
