Inhibition of CDK4-6 as a novel therapeutic option for neuroblastomaReport as inadecuate




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Cancer Cell International

, 15:76

First Online: 30 July 2015Received: 25 March 2015Accepted: 09 July 2015

Abstract

BackgroundNeuroblastoma 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.

MethodsIn 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.

ResultsMarked 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.

ConclusionSelective inhibition of CDK4-6 using palbociclib may provide a new therapeutic option for treating neuroblastoma.

KeywordsCell cycle Neuroblastoma Palbociclib Cyclin D1 Targeted therapy AbbreviationsCDK4-6cyclin D1 dependent kinases 4-6

CDCscell division cycle proteins

TOP2Atopoisomerase 2A

CCNE2cyclin E2

TK1thymidine kinase

GSK3βglycogen synthase kinase 3 β

FCSfetal calf serum

RT-qPCRreverse transcription-quantitative polymerase chain reaction

Electronic supplementary materialThe online version of this article doi:10.1186-s12935-015-0224-y contains supplementary material, which is available to authorized users.

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Author: Ali Rihani - Jo Vandesompele - Frank Speleman - Tom Van Maerken

Source: https://link.springer.com/article/10.1186/s12935-015-0224-y



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