Study on the Mechanism of Astragalus Polysaccharides on Cervical Cancer Based on Network Pharmacology

Abstract

Background: Astragalus polysaccharides (APS) is a natural phytochemical which has been extensively utilized for anti-tumor therapy over the past few years. However, its impact on cervical cancer (CC) has rarely been studied. Objective: To clarify the exact mechanism of anti-cancer effects of Astragalus polysaccharides (APS) on Cervical Cancer (CC), we screened differentially expressed genes (DEGs) from The Cancer Genome Atlas (TCGA) to construct the cancer network. Methods: Then we performed functional enrichment analysis with gene ontology (GO) and KEGG pathway analyses, constructed protein-protein interaction (PPI) network, and performed molecular docking (MD) analysis to identify the key gene for docking with APS. Further, we observed the effects of APS on cell proliferation, cell cycle, and apoptosis experiments in HeLa cells. qRT-PCR and western blot were used to detect the expression of target genes. Results: A total of 793 DEGs were screened using criteria, which included 541 genes that were up-regulated and 251 genes that were down-regulated. Using topological attributes for identifying critical targets, molecular docking (MD), and survival analyses, this study predicted the APS targets: POLO-like kinase 1(PLK1), Cyclin-cell division 20(CDC20), and Cyclin-dependent kinase 1 (CDK1), which regulated HeLa cells. The results of cell proliferation, cell cycle, and apoptosis experiments concluded that APS inhibited the development of HeLa cells in a concentration-dependent manner. Also, qRT-PCR and western blot experiments demonstrated that APS could significantly down-regulate the expression of PLK1, CDC20, and CDK1 in the CC cells. Conclusion: The result revealed that APS might have a therapeutic potential in treating CC and might permit intervention with treatments targeting PLK1, CDC20, and CDK1.