School of Life Science and Technology, Weifang Medical University, Weifang, 261053, China.
State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian, 116024, China.
J Nat Med. 2021 Sep;75(4):854-870. doi: 10.1007/s11418-021-01525-x. Epub 2021 May 27.
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.
黄芪多糖（APS）常被用作佐剂，其免疫调节活性可增强化疗药物在乳腺癌治疗中的疗效并降低其毒性。然而，APS 的其他协同作用机制尚不清楚。本研究旨在评估 APS 在体内对乳腺癌的直接抗肿瘤活性的潜在靶点和可能机制。进行了多种生物学检测以研究关键靶点的蛋白和 mRNA 表达水平。从 7 个基因表达数据集共检测到 116 个下调和 73 个上调的差异表达基因（DEGs）。从涉及体外 APS 抑制乳腺癌细胞系的每个特定生物学过程（BP、细胞周期、细胞增殖、细胞凋亡和死亡）的四个典型 DEG 相互作用（PPI）网络中获得了前十个枢纽基因。在上述四个 BP-PPI 网络中进一步鉴定出四个共同的 DEGs（EGFR、ANXA1、KIF14 和 IGF1），其中 EGFR 和 ANXA1 是与乳腺癌进展潜在相关的枢纽基因。生物学检测结果表明，APS 可下调乳腺癌细胞中 EGFR 的表达，同时显著增加 ANXA1 的表达。综上所述，本研究可能为乳腺癌的治疗提供潜在的分子治疗靶点和新的作用机制。
