Astragalus Polysaccharide Regulates EGFR and ANXA1 Expression to Inhibit Tumor Growth

Abstract

Background: Astragalus polysaccharide (APS) has been frequently used as an adjuvant agent responsible for its immunoregulatory activity to enhance efficacy and reduce toxicity of chemotherapy used in the management of breast cancer. However, the other synergism mechanism of APS remains unclear. Methods: The expression profiles of breast cancer biological data (E-GEOD-10780), (E-GEOD-65194), (E-GEOD-10810), (E-GEOD-42568), (E-GEOD-61304), (E-GEOD-7904) and (E-GEOD-15852) were retrieved from European bioinformatics institute (EBI) database to identify differentially expressed genes (DEGs). Gene Ontology and pathway enrichment analyses were carried out. The protein–protein interaction (PPI) networks of the DEGs were constructed by STRING online database. Finally, STRING was applied to construct the PPI networks of the DEGs associated with cell proliferation, cell cycle and cell apoptosis from GO enrichment analysis. Subsequently, hub and common genes that might be the potential targets and possible mechanism behind APS in vivo direct anti-tumor activity on breast cancer were identified. Meanwhile, we evaluated the mRNA and protein expression levels of these key targets using multiple biological analyses.Results: In total, 116 down-regulated and 73 up-regulated differential expressed genes (DEGs) were examined from seven gene expression datasets. Top ten hub genes were obtained in four typical protein-protein interaction (PPI) network of DEGs involved in each specific biological process (BP, cell cycle, cell proliferation, cell apoptosis and death) that was related to inhibitory activity of APS in vitro against breast cancer cell lines. Four common DEGs (EGFR, ANXA1, KIF14 and IGF1) were further identified in the above four BP-PPI networks, among which EGFR and ANXA1 were the hub genes that were potentially linked to the progression of breast cancer. The results of biological detections indicated that APS could down-regulated EGFR and up-regulated ANXA1 expression.Conclusion: In conclusion, the present study may provide potential molecular therapeutic targets and a new insight into the mechanism of APS against breast cancer.