Abstract
Background: Astragalus polysaccharides (APS), natural plant compounds, have recently emerged as a promising strategy for cancer treatment, but little is known concerning their effects on breast cancer (BC) tumorigenesis.Methods: We obtained breast cancer genetic data from The Cancer Genome Atlas (TCGA) database, network pharmacology to further clarify its biological properties. Survival analysis and molecular docking techniques were implemented for the final screening to obtain key target information. Our experiments focused on the detection of intervention effects of APS on BC cells (MCF-7 and MDA-MB-231), and quantitative RT-PCR (qRT-PCR) was used to assess the expression of key targets.Results: A total of 1,439 differentially expressed genes (DEGs) were identified by TCGA and used to build disease networks. Module analysis, gene ontology and pathway analysis revealed characteristic of the DEGs network. Topological properties were used to identify key targets, survival analysis and molecular docking finally found that the targets of APS regulation of BC cells may be CCNB1, CDC6, and p53. Through cell viability, migration and invasion assays, we found that APS interferes with the development of breast cancer in MCF7 and MDA-MB-231 cells in a dose-dependent manner. Furthermore, qRT-PCR verification suggested that the expression of CCNB1 and CDC6 in breast cancer cells was significantly downregulated in response to APS, while expression of the tumor suppressor gene P53 was significantly increased.Conclusion: Results of this study suggest therapeutic potential for APS in BC treatment, possibly through interventions with CCNB1, CDC6, and P53. Furthermore, these findings illustrate the feasibility of using network pharmacology to connect large-scale target data as a way to discover the mechanism of natural products interfering with disease.
Highlights
Breast cancer (BC) is one of the most common cancers and remains a serious health threat for women, comprising ∼30% of cancer cases in women each year [1]
Since the information was retrieved from The Cancer Genome Atlas (TCGA) database, a public data set, further ethical approval was not needed for our research
Enrichment results show that: Molecular function participates in cellular activities, such as calcium ion binding, transcription factor activity, sequence-specific DNA binding, cytoskeletal protein binding and peptidase activity; Biological process is mainly enriched in cell-cell signaling, cell cycle, ion transport, and cell adhesion and other physiological processes related to cell growth, division, and proliferation; Cellular component is associated with the extracellular space, plasma membrane binding, extracellular regions, and components of the plasma membrane
Summary
Breast cancer (BC) is one of the most common cancers and remains a serious health threat for women, comprising ∼30% of cancer cases in women each year [1]. Survival rates of breast cancer patients have gradually improved thanks to new therapeutic strategies, many patients still face recurrence, and long-term mortality remains high. It is necessary to identify new therapeutic agents or emerging targets. Small molecular compounds from natural products have historically been used for disease intervention, and as valuable sources of lead compounds for drug development. The multi-target interventional properties of natural products seem to fit this therapeutic concept. With the continuous development of natural products as effective candidates for drug selection, comprehensive determination of small molecule multi-target interaction spectrums have become increasingly necessary. Astragalus polysaccharides (APS), natural plant compounds, have recently emerged as a promising strategy for cancer treatment, but little is known concerning their effects on breast cancer (BC) tumorigenesis
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