Mechanisms of dihydromyricetin against hepatocellular carcinoma elucidated by network pharmacology combined with experimental validation.
Pharm Biol
; 61(1): 1108-1119, 2023 Dec.
Article
em En
| MEDLINE
| ID: mdl-37462387
ABSTRACT
CONTEXT Dihydromyricetin (DMY) is extracted from vine tea, a traditional Chinese herbal medicine with anti-cancer, liver protection, and cholesterol-lowering effects. OBJECTIVE:
This study investigated the mechanism of DMY against hepatocellular carcinoma (HCC). MATERIALS ANDMETHODS:
Potential DMY, HCC, and cholesterol targets were collected from relevant databases. PPI networks were created by STRING. Then, the hub genes of co-targets, screened using CytoHubba. GO and KEGG pathway enrichment, were performed by Metascape. Based on the above results, a series of in vitro experiments were conducted by using 40-160 µM DMY for 24 h, including transwell migration/invasion assay, western blotting, and Bodipy stain assay.RESULTS:
Network pharmacology identified 98 common targets and 10 hub genes of DMY, HCC, and cholesterol, and revealed that the anti-HCC effect of DMY may be related to the positive regulation of lipid rafts. Further experiments confirmed that DMY inhibits the proliferation, migration, and invasion of HCC cells and reduces their cholesterol levels in vitro. The IC50 is 894.4, 814.4, 467.8, 1,878.8, 151.8, and 156.9 µM for 97H, Hep3B, Sk-Hep1, SMMC-7721, HepG2, and Huh7 cells, respectively. In addition, DMY downregulates the expression of lipid raft markers (CAV1, FLOT1), as well as EGFR, PI3K, Akt, STAT3, and Erk. DISCUSSION ANDCONCLUSION:
The present study reveals that DMY suppresses EGFR and its downstream pathways by reducing cholesterol to disrupt lipid rafts, thereby inhibiting HCC, which provides a promising candidate drug with low toxicity for the treatment of HCC.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Hepatocelular
/
Neoplasias Hepáticas
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Pharm Biol
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China