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Updated: Nov 1, 2025
Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
Selected using bioinformatics and molecular docking analyses, PHA-793887 is effective against osteosarcoma
Bo Wu1, Wenzhuo Yang2, Zhaoyu Fu1
1Department of Orthopaedics, The First Hospital of Jilin University, Changchun, China.
Abstract:
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.
Insights
This study identified cyclin-dependent kinase 1 (CDK1) as a prognostic target in osteosarcoma. The drug PHA-793887 showed promise in preclinical models by inhibiting CDK1, reducing tumor cell viability, and inducing apoptosis.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Osteosarcoma is a primary bone cancer with limited treatment options.
- Identifying novel prognostic and therapeutic targets is crucial for improving patient outcomes.
Purpose of the Study:
- To identify novel prognostic and therapeutic targets for osteosarcoma.
- To evaluate the potential of PHA-793887 as a CDK1 inhibitor for osteosarcoma treatment.
Main Methods:
- Gene expression profiling of osteosarcoma and control tissues (GSE42352 dataset).
- Bioinformatic analyses including Gene Ontology, KEGG, GSEA, and PPI networks.
- In vitro assays (MTT, colony formation, scratch, flow cytometry, Western blotting, ELISA) to assess PHA-793887 efficacy.
Main Results:
- Lower mRNA levels of CDK1 and topoisomerase II alpha correlated with better patient prognoses.
- PHA-793887 demonstrated high binding affinity for CDK1 and reduced osteosarcoma cell viability, clonogenicity, and migration in vitro.
- PHA-793887 induced dose-dependent apoptosis and decreased CDK1 expression in osteosarcoma cells.
Conclusions:
- CDK1 is a potential prognostic biomarker and therapeutic target in osteosarcoma.
- PHA-793887 exhibits preclinical efficacy against osteosarcoma by inhibiting CDK1 and warrants further investigation as a novel therapeutic agent.
