Cytotoxicity and growth-inhibiting activity of Astragalus polysaccharides against breast cancer via the regulation of EGFR and ANXA1

Abstract

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. This study was performed to evaluate the potential targets and possible mechanism behind APS in vivo direct anti-tumor activity on breast cancer. Multiple biological detections were conducted to investigate the protein and mRNA expression levels of key targets. In total, 116 down-regulated and 73 up-regulated differential expressed genes (DEGs) were examined from 7 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 the expression of EGFR in breast cancer cells was down-regulated, while the expression of ANXA1 was markedly increased in response to APS. In conclusion, the present study may provide potential molecular therapeutic targets and a new insight into the mechanism of APS against breast cancer.

Keywords: ANXA1; Astragalus polysaccharide; Cell apoptosis; Cell cycle; Cytotoxicity; EGFR.