[Molecular mechanism of Puerariae Lobatae Radix in treatment of hepatocellular carcinoma based on network pharmacology].
Zhongguo Zhong Yao Za Zhi
; 45(17): 4089-4098, 2020 Sep.
Article
em Zh
| MEDLINE
| ID: mdl-33164393
ABSTRACT
To investigate the potential mechanism of Puerariae Lobatae Radix in the treatment of hepatocellular carcinoma by network pharmacology and in vitro cell experiment. The main active components of Puerariae Lobatae Radix and their predicted targets were obtained from TCMSP, and the disease targets were obtained from GeneCards database. The disease and drug prediction targets were intersected to select the common potential therapeutic targets. The "compound-target-disease" network diagram was constructed in Cytoscape 3.7.1, and the common targets were input into the STRING database to build the PPI network of proteins interaction. GO function and KEGG pathway enrichment analysis on effective targets were performed by using R software. Autodock vina 1.1.2 was used for molecular docking. Finally, the core targets and pathways were preliminarily verified by in vitro experiments. The proliferation of human hepatocellular carcinoma cells was detected by CCK-8 and EDU enzyme staining, and the expressions of PTEN, PDK1, Akt and GSK3 were detected by Western blot. In this study, 10 components of Puerariae Lobatae Radix(9 components involved in hepatocellular carcinoma-related targets and signaling pathways), and 149 hepatocellular carcinoma-related targets and 156 signaling pathways were screened out. The results of network analysis indicated that Puerariae Lobatae Radix may play an anti-hepatocellular carcinoma effect on key targets, such as Akt, IL6, MAPK3, EGFR, and key pathways, such as PI3 K-Akt. The results of molecular docking indicated that puerarin, genistein and daidzein had a good binding ability with the key targets such as AKT1, MAPK3, MAPK1 and CASP3, and puerarin had the lowest Vina score with AKT1 and MAPK3 and also similar to them. In vitro cell experiments confirmed that puerarin has a significantly inhibitory effect on the proliferation of human hepatocellular carcinoma cells. Western blot results showed that puerarin could increase the phosphorylation of PTEN in human hepatocellular carcinoma cells through the PTEN/Akt/GSK3ß signaling pathway, and the phosphorylation level of its downstream Akt decreased. This series of studies confirm that puerarin can treat hepatocellular carcinoma by blocking PTEN/Akt/GSK3ß cellular signaling pathway, so as to provide ideas for subsequent studies for the molecular mechanism of puerarin in the treatment of liver cancer.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Medicamentos de Ervas Chinesas
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Carcinoma Hepatocelular
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Pueraria
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Neoplasias Hepáticas
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
Zh
Ano de publicação:
2020
Tipo de documento:
Article