Systems pharmacology in combination with proteomics reveals underlying mechanisms of Xihuang pill against triple-negative breast cancer. Issue 1 (1st January 2020)

• Record Type: Journal Article
• Authors: Xu, Xingchao; Zhang, Jimei; Zhang, Zhenhua; Wang, Meng; Liu, Yaping; Li, Xiangqi
• Is Part Of: Bioengineered. Volume 11:Issue 1(2020)
• Page Start: 1170
• Page End: 1188
• Publication Date: 2020-01-01
• Subjects: Triple-negative breast cancer -- traditional Chinese medicine -- Xihuang pill -- systems pharmacology -- proteomics; Biomedical engineering -- Periodicals; Biotechnology -- Periodicals; Microbiology -- Periodicals; 660.6
• DOI: 10.1080/21655979.2020.1834726
• Languages: English
• ISSNs: 2165-5987

Abstract

ABSTRACT: Xihuang pill (XHP), a traditional Chinese herbal formula, has been clinically used as an adjuvant therapy against triple-negative breast cancer (TNBC) via inhibiting cancer cell invasion and proliferation, as well as promoting cancer cell apoptosis. However, its anti-TNBC bio-active ingredients and possible mechanisms are still unclear. Herein, the hub bio-active compounds and underlying mechanisms of XHP against TNBC were systematically elucidated by integrating systems pharmacology approach and in vitro proteomics analysis. Using systems pharmacology analysis and molecular docking evaluation, 28 bio-active compounds and 10 potential therapeutic targets of XHP were identified. Functional analysis showed that the core therapeutic targets against TNBC were mainly involved in epidermal growth factor receptor (EGFR)-phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway to prevent cancer cell proliferation and angiogenesis, as well as to enhance cancer cell apoptosis. The in vitro proteomics analysis identified 153 differentially expressed proteins (DEPs), including HASP90AA1, AKT1, and EGFR, which were also identified as therapeutic targets against TNBC through systems pharmacology analysis. Protein function analysis showed that the DEPs were mainly involved in PI3K-AKT signaling pathway, which was consistent with the result of systems pharmacology, suggesting the reliability of systems pharmacology analysis. Taken together, these findings uncover the underlying mechanism of XHP against TNBC, and provide a scientific method for the rational development of traditional Chinese medicine. Graphical_abstract: