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.
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.
A total of 793 DEGs were screened using criteria, which included 541 genes that were upregulated 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 concentrationdependent 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.
The result revealed that APS might have a therapeutic potential in treating CC and might permit intervention with treatments targeting PLK1, CDC20, and CDK1.
目的:阐明黄芪多糖(APS)对宫颈癌(CC)的抗癌作用的确切机制。我们从癌症基因组图谱(TCGA)中筛选差异表达基因(DEGs),构建癌症网络。
方法:然后我们用基因本体论(GO)和KEGG通路分析进行功能富集分析,构建的蛋白质-蛋白质相互作用(PPI)网络,并进行了分子对接(MD)分析,以确定与APS对接的关键基因。Further,我们观察到APS对细胞增殖的影响,细胞周期,和HeLa细胞凋亡实验。qRT-PCR和westernblot检测目标基因的表达。
结果:使用标准筛选了总共793个DEG,其中包括541个上调的基因和251个下调的基因。使用拓扑属性来识别关键目标,分子对接(MD),和生存分析,这项研究预测了APS的靶标:POLO样激酶1(PLK1),细胞周期蛋白细胞分裂20(CDC20),和细胞周期蛋白依赖性激酶1(CDK1),调节HeLa细胞。细胞增殖的结果,细胞周期,和凋亡实验得出结论,APS以浓度依赖的方式抑制HeLa细胞的发育。此外,qRT-PCR和Westernblot实验表明,APS可以显着下调CC细胞中PLK1,CDC20和CDK1的表达。
结论:结果显示,APS可能具有治疗CC的潜在治疗潜力,并且可能允许对靶向PLK1、CDC20和CDK1的治疗进行干预。