Multiple CDK Inhibitor Dinaciclib Suppresses Neuroblastoma Growth Via Inhibiting CDK2 and CDK9 Activity

Overview

Journal Sci Rep

Specialty Science

Date 2016 Jul 6

PMID 27378523

Citations 42

Authors

Zhenghu Chen

Zhenyu Wang

Jonathan C Pang

Yang Yu

Shayahati Bieerkehazhi

Jiaxiong Lu

Ting Hu

Yanling Zhao

Xin Xu

Hong Zhang

Joanna S Yi

Shangfeng Liu

Jianhua Yang

Affiliations

Soon will be listed here.

Abstract

Neuroblastoma (NB), the most common extracranial solid tumor of childhood, is responsible for approximately 15% of cancer-related mortality in children. Aberrant activation of cyclin-dependent kinases (CDKs) has been shown to contribute to tumor cell progression in many cancers including NB. Therefore, small molecule inhibitors of CDKs comprise a strategic option in cancer therapy. Here we show that a novel multiple-CDK inhibitor, dinaciclib (SCH727965, MK-7965), exhibits potent anti-proliferative effects on a panel of NB cell lines by blocking the activity of CDK2 and CDK9. Dinaciclib also significantly sensitized NB cell lines to the treatment of chemotherapeutic agents such as doxorubicin (Dox) and etoposide (VP-16). Furthermore, dinaciclib revealed in vivo antitumor efficacy in an orthotopic xenograft mouse model of two NB cell lines and blocked tumor development in the TH-MYCN transgenic NB mouse model. Taken together, this study suggests that CDK2 and CDK9 are potential therapeutic targets in NB and that abrogating CDK2 and CDK9 activity by small molecules like dinaciclib is a promising strategy and a treatment option for NB patients.

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