Selected using bioinformatics and molecular docking analyses, PHA-793887 is effective against osteosarcoma.

骨肉瘤 对接(动物) 计算生物学 化学 生物信息学
作者
Bo Wu,Wenzhuo Yang,Zhaoyu Fu,Haoqun Xie,Zhen Guo,Daqun Liu,Junliang Ge,Sheng Zhong,Luwei Liu,Jingyi Liu,Dong Zhu
出处
期刊:Aging [Impact Journals LLC]
卷期号:13 (12): 16425-16444
标识
DOI:10.18632/aging.203165
摘要

To identify novel prognostic and therapeutic targets for osteosarcoma patients, we compared the gene expression profiles of osteosarcoma and control tissues from the GSE42352 dataset in the Gene Expression Omnibus. Differentially expressed genes were subjected to Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Enrichment and protein-protein interaction network analyses. Survival curve analyses indicated that osteosarcoma patients with lower mRNA levels of cyclin-dependent kinase 1 (CDK1) and topoisomerase II alpha had better prognoses. Various computer-aided techniques were used to identify potential CDK1 inhibitors for osteosarcoma patients, and PHA-793887 was predicted to be a safe drug with a high binding affinity for CDK1. In vitro, MTT and colony formation assays demonstrated that PHA-793887 reduced the viability and clonogenicity of osteosarcoma cells, while a scratch assay suggested that PHA-793887 impaired the migration of these cells. Flow cytometry experiments revealed that PHA-793887 dose-dependently induced apoptosis in osteosarcoma cells. Western blotting and enzyme-linked immunosorbent assays indicated that CDK1 expression in osteosarcoma cells declined with increasing PHA-793887 concentrations. These results suggest that PHA-793887 could be a promising new treatment for osteosarcoma.

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