Doxorubicin activates the Notch signaling pathway in osteosarcoma

Abstract

Notch signaling is critical in various biological processes, including cell proliferation, differentiation and apoptosis. Furthermore, accumulating evidence indicated that aberrant Notch signaling has a tumor-promoting function in osteosarcoma. However, the effect of the conventional chemotherapeutic agent, doxorubicin, on Notch signaling remains unclear. In the present study, osteosarcoma cells were treated with various concentrations of doxorubicin and the effect on Notch signaling was analyzed. A cytostatic dose of doxorubicin (<0.5 μM) was identified to significantly activate the Notch signaling pathway in a dose-dependent manner (P<0.01), as demonstrated by the elevated expression levels of Notch target genes. However, a toxic dose of doxorubicin (≥0.5 μM) significantly inhibited the Notch signaling pathway (P<0.01). These results indicated a significant correlation between doxorubicin administration and the Notch signaling pathway. Therefore, the present study supports further investigation into Notch and osteosarcoma chemoresistance.