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Research Paper|Volume 13, Issue 12|pp 16425—16444

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

Bo Wu1, Wenzhuo Yang2, Zhaoyu Fu1, Haoqun Xie2, Zhen Guo2, Daqun Liu3, Junliang Ge2, Sheng Zhong4, Luwei Liu5, Jingyi Liu5, Dong Zhu1
  • 1Department of Orthopaedics, The First Hospital of Jilin University, Changchun, China
  • 2Clinical College, Jilin University, Changchun, China
  • 3Department of Liver and Gallbladder Surgery, The First Hospital of Jilin University, Changchun, China
  • 4Department of Neurosurgery, Cancer Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
  • 5Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA
Received: January 29, 2021Accepted: May 17, 2021Published: June 21, 2021
https://doi.org/10.18632/aging.203165

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.