Open AccessDoxorubicin Inhibits Proliferation of Osteosarcoma Cells Through Upregulation of the Notch Signaling Pathway
Author(s) -
Peng Ji,
Ling Yu,
Weichun Guo,
Hongjun Mei,
Xiaoju Wang,
Chen Hu,
Shuo Fang,
Jian Yang
Publication year - 2015
Publication title -
oncology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 57
eISSN - 1555-3906
pISSN - 0965-0407
DOI - 10.3727/096504015x14343704124340
Subject(s) - notch signaling pathway , hes1 , doxorubicin , osteosarcoma , apoptosis , gene knockdown , cancer research , signal transduction , cell growth , viability assay , microbiology and biotechnology , small interfering rna , downregulation and upregulation , biology , transfection , cell culture , chemotherapy , biochemistry , gene , genetics
Doxorubicin plays a major role in the treatment of osteosarcoma disorders. The Notch signaling pathway exerts various biological functions, including cell proliferation, differentiation, and apoptosis. In the present study, we investigated the effects of different doses of doxorubicin on proliferation and apoptosis of osteosarcoma cells with or without Notch signaling. Results found that cellular viability was downregulated while caspase 3 activity and expression were promoted in osteosarcoma cells following treatment with various doses of doxorubicin for 24, 48, and 72 h, and the effects showed a dose- and time-dependent manner. Furthermore, it was found that various doses of doxorubicin activated the Notch signaling pathway, shown by the elevated expression of Notch target genes NOTCH1, HEY1, HES1, AND HES5. It was further proved that, after small interfering RNA (siRNA)-mediated knockdown of Notch, the effects of doxorubicin on the viability and apoptosis of osteosarcoma cells were significantly reduced. It was indicated that doxorubicin treatment reduced the proliferation and promoted the apoptosis of osteosarcoma cells, and this effect was mediated by the Notch signaling pathway.