Clinically relevant doses of chemotherapy agents reversibly block formation of glioblastoma neurospheres

被引:22
作者
Mihaliak, Alicia M. [1 ]
Gilbert, Candace A. [1 ]
Li, Li [1 ]
Daou, Marie-Claire [1 ]
Moser, Richard P. [2 ]
Reeves, Andrew [3 ]
Cochran, Brent H. [3 ]
Ross, Alonzo H. [1 ]
机构
[1] Univ Massachusetts, Dept Biochem & Mol Pharmacol, Sch Med, Worcester, MA 01605 USA
[2] Univ Massachusetts, Dept Neurosurg, Sch Med, Worcester, MA 01605 USA
[3] Tufts Univ, Sch Med, Dept Physiol, Boston, MA 02111 USA
基金
美国国家卫生研究院;
关键词
Chemotherapy; Cancer stem cells; DNA damage; Temozolomide; BCNU; Glioblastoma; Neurosphere; NEURAL STEM-CELLS; TUMOR-INITIATING CELLS; MALIGNANT GLIOMA-CELLS; GROWTH-FACTOR RECEPTOR; ADULT-MOUSE BRAIN; PROGENITOR CELLS; TEMOZOLOMIDE; CANCER; PHARMACOKINETICS; IDENTIFICATION;
D O I
10.1016/j.canlet.2010.04.005
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Glioblastoma patients have a poor prognosis, even after surgery, radiotherapy, and chemotherapy with temozolomide or 1,3-bis(2-chloroethy)-1-nitrosourea. We developed an in vitro recovery model using neurosphere cultures to analyze the efficacy of chemotherapy treatments, and tested whether glioblastoma neurosphere-initiating cells are resistant. Concentrations of chemotherapy drugs that inhibit neurosphere formation are similar to clinically relevant doses. Some lines underwent a transient cell cycle arrest and a robust recovery of neurosphere formation. These results indicate that glioblastoma neurospheres can regrow after treatment with chemotherapy drugs. This neurosphere recovery assay will facilitate studies of chemo-resistant subpopulations and methods to enhance glioblastoma therapy. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:168 / 177
页数:10
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