Clinically relevant doses of chemotherapy agents reversibly block formation of glioblastoma neurospheres.
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.
Mihaliak
Alicia M
AM
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, USA.
Gilbert
Candace A
CA
Li
Li
L
Daou
Marie-Claire
MC
Moser
Richard P
RP
Reeves
Andrew
A
Cochran
Brent H
BH
Ross
Alonzo H
AH
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D002330:Carmustine / Q000627:therapeutic use; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D016923:Cell Death; D002455:Cell Division; D045744:Cell Line, Tumor; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005091:Exons; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000532:radiotherapy / Q000601:surgery; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D000077204:Temozolomide; D014183:Transplantation, Heterologous; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D017931:DNA Primers; D018076:DNA, Complementary; D003606:Dacarbazine; D002330:Carmustine; D000077204:Temozolomide