Title
Clinically relevant doses of chemotherapy agents reversibly block formation of glioblastoma neurospheres
UMMS Affiliation
Department of Biochemistry and Molecular Pharmacology
Date
10-28-2010
Document Type
Article
Medical Subject Headings
Animals; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Carmustine; Cell Adhesion; Cell Culture Techniques; Cell Death; Cell Division; Cell Line, Tumor; DNA Primers; DNA, Complementary; Dacarbazine; Exons; Glioblastoma; Humans; Mice; Mice, Nude; Neoplasm Recurrence, Local; Prognosis; Transplantation, Heterologous; Treatment Outcome
Abstract
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.
Rights and Permissions
Citation: Cancer Lett. 2010 Oct 28;296(2):168-77.