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

被引：36

作者：

Rihani, Ali ^{[1
]}

Vandesompele, Jo ^{[1
]}

Speleman, Frank ^{[1
]}

Van Maerken, Tom ^{[1
]}

机构：

[1] Univ Ghent, Ctr Med Genet, B-9000 Ghent, Belgium

来源：

CANCER CELL INTERNATIONAL | 2015年 / 15卷

关键词：

Cell cycle; Neuroblastoma; Palbociclib; Cyclin D1; Targeted therapy; CELL-CYCLE ARREST; KINASE INHIBITOR; TARGET; CANCER; PHOSPHORYLATION; LOCALIZATION; APOPTOSIS; D1;

D O I：

10.1186/s12935-015-0224-y

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：8

共 28 条

[1] Polo-Like Kinase 1 is a Therapeutic Target in High-Risk Neuroblastoma [J].