Anti-breast Cancer Effect and Molecular Mechanism of Rhein Based on Network Pharmacology and Animal Experiments
10.13748/j.cnki.issn1007-7693.20222507
- VernacularTitle:基于网络药理学和动物实验探讨大黄酸抗乳腺癌作用与分子机制
- Author:
Shuang ZHENG
1
;
Yang XIONG
2
Author Information
1. Taizhou Traditional Chinese Medicine Hospital, Taizhou 318000, China
2. College of Pharmacy, Zhejiang Chinese Medical University, Hangzhou 311402, China
- Publication Type:Journal Article
- Keywords:
rhein;breast cancer ;network pharmacology; target ;signal pathway
- From:
Chinese Journal of Modern Applied Pharmacy
2024;41(12):1648-1654
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE :To explore the anti-tumor effect and molecular mechanism prediction of rhein by network pharmacology and animal experiments, and provide experimental basis and theoretical guidance for further study of the molecular mechanism of rhein combined with doxorubicin in anti-breast cancer.
METHODS
The tumor xenograft in mouse model was constructed to investigate the anti-breast cancer effect of rhein combined with doxorubicin. And the Pubchem database, Swiss Target Prediction database, STITCH database, TCMSP database were used to obtain rhein components and action targets, the OMIM, TTD, Genecards and other databases was used to obtain breast cancer disease targets, the "component-disease-target" network and protein-protein interaction(PPI) network was constructed by Cytoscape 3.8.2 to perform topological analysis, and obtain potential targets; the Bioconductor bioinformatics package based on R software was used for GO functional annotation and KEGG enrichment analysis, to screen for possible mechanisms by which drugs act on diseases.
RESULTS
The pharmacodynamic results in vivo showed that rhein could enhance the anti-breast cancer effect of doxorubicin. Through database analysis, 64 targets of rhein components, 1 839 targets of breast cancer disease, and 31 targets of drug and disease intersection were obtained. PPI network analysis and KEGG pathway enrichment analysis showed that multiple key target proteins MMP9, CASP3, VEGFA, MAPK8, etc., as well as key signaling pathways such as interleukin-17, tumor necrosis factor, cell proliferation and apoptosis, were closely related to breast cancer.
CONCLUSION
Rhein can enhance the anti-breast cancer effect of doxorubicin by inhibiting tumor angiogenesis, down regulating estrogen receptor, inducing apoptosis, and participating in tumor extracellular matrix remodeling.