Abstract

Osteosarcoma (OS) primarily accurs in adolescents, and is more prevalent in males than females. It is characteristics by local invasive growth and early pulmonary metastases. Nanoparticles (NPs) have emerged as a promising alternative to traditional chemotherapeutic drugs due to their high selectivity and effectiveness. Previous studies have demonstrated the potential of zinc oxide nanoparticles (ZnO NPs) as a treatment for various tumors except OS. In this study, we use RNA-seq analysis to investigate the underlying biological mechanism involved in the process of ZnO NPs-treated different types of OS cell lines. We identified 928 differentially expressed genes (DEGs) in both 143B and MG-63 cells, and we validated the expression of the eight most significant DEGs using RT-qPCR. Gene Ontology (GO) analysis displayed regulation of transcription factor on nucleic acid binding in molecular function term, and extracellular space in cellular components term in both OS cell lines. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed the co-enrichment of the MAPK, Toll-like receptor, and NF-κB pathways in both OS cell lines. Protein–protein interaction (PPI) analysis highlighted the involvement of HMOX1, MAFB, CXCL10, and CXCL11 in various biological processes in OS cells treated with ZnO NPs. Furthermore, we confirmed the key protein molecules in the differential signaling pathways of both OS cell lines using Western Blot (WB). Our findings shed light on the potential antitumor mechanisms and exploitable bioeffects of ZnO NPs in the treatment of OS. This study provides more targets and possible mechanisms for the treatment of ZnO NPs, as well as more theoretical basis for the treatment of OS.

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