title: 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.
authors.affiliation: Department of Orthopaedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Mei
authors.affiliation: Department of Orthopaedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Orthopaedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Ji
authors.affiliation: Department of Orthopaedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Orthopaedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Fang
authors.affiliation: Department of Orthopaedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Weichun
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Orthopaedics, Fifth Hospital of Wuhan, Hubei 430050, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Xuanyin
authors.initials: X
authors.lastname: Chen
keywords: Notch signaling pathway; doxorubicin; osteosarcoma