Literature DB >> 25107642

Dasatinib suppression of medulloblastoma survival and migration is markedly enhanced by combining treatment with the aurora kinase inhibitor AT9283.

William Petersen1, Jingbo Liu1, Liangping Yuan1, Hongying Zhang1, Matthew Schneiderjan2, Yoon-Jae Cho3, Tobey J MacDonald4.   

Abstract

Medulloblastoma (MB) expresses Src kinase, while aurora kinase A overexpression correlates with poor survival. We thus investigated novel combination treatment with dasatinib and AT9283, inhibitors of Src and aurora kinase, respectively, on MB growth in vitro and in vivo. Treatment with each drug significantly reduced cell viability and combined treatment markedly potentiated this response. AT9283 induced p53 expression, autophagy, and G2/M cell-cycle arrest, while combined treatment induced S phase arrest. Dasatinib treatment caused tumor regression in vivo. Activated Src was detected in 44% MB analyzed. We conclude that further evaluation of this combination therapy for MB is highly warranted.
Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Entities:  

Keywords:  Aurora kinase; Dasatinib; Medulloblastoma; Survival

Mesh：

Substances：

Year:  2014        PMID： 25107642      PMCID： PMC4179499          DOI： 10.1016/j.canlet.2014.07.038

Source DB:  PubMed          Journal:  Cancer Lett        ISSN： 0304-3835            Impact factor:   8.679


  41 in total

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