Neuroblastoma (NB), which accounts for about 15% of cancer-related mortality in children, is the most common extracranial malignant neoplasm in children. Elevated level of proteasome activity promotes cancer development and the inhibition of proteasome activity is a promising strategy for cancer treatment. Therefore, targeting proteasome by small molecule inhibitors may be a viable option for NB therapy. Here in this study, we show that a novel proteasome inhibitor Carfilzomib (CFZ) exerts anti-tumor effect on NB. CFZ caused decreased cell viability and attenuated colony formation ability of a subset of NB cell lines. CFZ induced cell apoptosis in NB cells. Moreover, CFZ enhanced the cytotoxic effect of doxorubicin (Dox) on NB cells and Dox-induced p38 and JNK phosphorylation. In addition, CFZ inhibited Dox-induced NF-κB activation by stabilizing the protein level of IκBa. Furthermore, CFZ induced apoptosis and augmented Dox-induced apoptosis in NB tumor cells in orthotopic xenograft mouse models. In summary, our study suggests that proteasome is a therapeutic target in NB and proteasome inhibition by CFZ is a potential therapeutic strategy for treating NB patients.
CITATION STYLE
Guan, S., Zhao, Y., Lu, J., Yu, Y., Sun, W., Mao, X., … Yang, J. (2016). Second-generation proteasome inhibitor carfilzomib sensitizes neuroblastoma cells to doxorubicin-induced apoptosis. Oncotarget, 7(46), 75914–75925. https://doi.org/10.18632/oncotarget.12427
Mendeley helps you to discover research relevant for your work.