Research Paper Volume 13, Issue 12 pp 16425—16444
Selected using bioinformatics and molecular docking analyses, PHA-793887 is effective against osteosarcoma
- 1 Department of Orthopaedics, The First Hospital of Jilin University, Changchun, China
- 2 Clinical College, Jilin University, Changchun, China
- 3 Department of Liver and Gallbladder Surgery, The First Hospital of Jilin University, Changchun, China
- 4 Department of Neurosurgery, Cancer Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- 5 Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA
Received: January 29, 2021 Accepted: May 17, 2021 Published: June 21, 2021
https://doi.org/10.18632/aging.203165How to Cite
Copyright: © 2021 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
Abbreviations
AURKA: Aurora kinase A; CDK1: cyclin-dependent kinase 1; DEG: differentially expressed gene; GO: Gene Ontology; GSEA: Gene Set Enrichment Analysis; KEGG: Kyoto Encyclopedia of Genes and Genomes; MAD2L1: mitotic arrest deficient 2-like 1; PPI: protein protein interaction; qRT-PCR: quantitative real-time polymerase chain reaction; RRM2: ribonucleotide reductase subunit M2; TOP2A: topoisomerase II alpha.