Systemic pharmacological verification of Salvia miltiorrhiza-Ginseng Chinese herb pair in inhibiting spontaneous breast cancer metastasis

Abstract

Breast cancer is the most commonly diagnosed cancer in the world, and metastasis is often the main cause of death in breast cancer patients. Salvia miltiorrhiza -Ginseng (SG) herb pair is clinically used for the treatment of cardiovascular diseases and cancers. However, the pharmacological action of this pair on breast cancer is yet unclear. In this study, a spontaneous metastasis model of breast cancer was constructed to assess the therapeutic value of SG. After administration of different doses of SG, the results showed that although it did not significantly inhibit tumor growth, high-dose SG administration could inhibit tumor metastasis. Then, based on systematic pharmacology combined with Gene Expression Omnibus (GEO) database, potential targets of drugs were identified such as vascular endothelial growth factor A (VEGFA), matrix metalloproteinase (MMP9), prostaglandin endoperoxide synthase2 (PTGS2), etc. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analysis revealed that these targets were related to cytokine-mediated signaling pathway, cell migration and other biological processes and signaling pathways such as PI3K/Akt, etc. The systematic pharmacology analysis showed that SG effectively inhibited the VEGFA and MMP9-mediated biological events such as angiogenesis, epithelial-mesenchymal transition (EMT) and impaired tumor metastasis. Overall, our research aimed to provide new ideas for the treatment of breast cancer lung metastasis in traditional Chinese medicine.