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Inhibition of CDK4/6 as a novel therapeutic option for neuroblastoma

BACKGROUND: Neuroblastoma is a neural crest-derived tumor and is the most common cancer in children less than 1 year of age. We hypothesized that aberrations in genes that control the cell cycle could play an important role in the pathogenesis of neuroblastoma and could provide a tractable therapeut...

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Detalles Bibliográficos
Autores principales: Rihani, Ali, Vandesompele, Jo, Speleman, Frank, Van Maerken, Tom
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4518532/
https://www.ncbi.nlm.nih.gov/pubmed/26225123
http://dx.doi.org/10.1186/s12935-015-0224-y
Descripción
Sumario:BACKGROUND: Neuroblastoma is a neural crest-derived tumor and is the most common cancer in children less than 1 year of age. We hypothesized that aberrations in genes that control the cell cycle could play an important role in the pathogenesis of neuroblastoma and could provide a tractable therapeutic target. METHODS: In this study, we screened 131 genes involved in cell cycle regulation at different levels by analyzing the effect of siRNA-mediated gene silencing on the proliferation of neuroblastoma cells. RESULTS: Marked reductions in neuroblastoma cellular proliferation were recorded after knockdown of CCND1 or PLK1. We next showed that pharmacological inhibition of cyclin D1 dependent kinases 4/6 (CDK4/6) with PD 0332991 (palbociclib) reduced the growth of neuroblastoma cell lines, induced G1 cell cycle arrest, and inhibited the cyclin D1-Rb pathway. CONCLUSION: Selective inhibition of CDK4/6 using palbociclib may provide a new therapeutic option for treating neuroblastoma. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12935-015-0224-y) contains supplementary material, which is available to authorized users.