Anti-breast Cancer Effect and Molecular Mechanism of Rhein Based on Network Pharmacology and Animal Experiments

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.