Sphingosine kinase 1 contributes to doxorubicin resistance and glycolysis in osteosarcoma.

Abstract

Osteosarcoma (OS) is one of the most common and aggressive malignancies in children and adolescents worldwide. Sphingosine kinase 1 (SphK1) has recently been reported to serve a role in OS progression. The present study aimed to investigate the role of SphK1 in the development of chemoresistance and glycolysis in OS cell lines. SphK1 expression levels in OS cell lines (U2OS, MG63 and SaoS2) were analyzed using western blotting and reverse transcription-quantitative PCR (RT-qPCR). A cell survival assay was conducted to determine doxorubicin-resistance in OS cells, and glycolysis was also evaluated. SphK1 expression was increased in the U2OS and SaoS2 cell lines, and both cell lines were more resistant to doxorubicin when compared with the MG63 cell line. SphK1 knockdown or overexpression altered doxorubicin resistance and the viability of OS cell lines. In addition, hypoxia inducible factor-1α (HIF-1α) expression was positively associated with SphK1 expression, and partly mediated SphK1-induced effects on doxorubicin resistance and glycolysis. The present study suggested that SphK1 participated in the development of doxorubicin resistance and contributed to glycolysis in OS cells by regulating HIF-1α expression. However, further studies investigating the application of SphK1 associated therapies for patients with OS are required.