Clinically relevant doses of chemotherapy agents reversibly block formation of glioblastoma neurospheres
Department of Biochemistry and Molecular Pharmacology
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
Biochemistry, Biophysics, and Structural Biology | Cancer Biology | Pharmacology, Toxicology and Environmental Health
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.
Cancer Lett. 2010 Oct 28;296(2):168-77.
Mihaliak AM, Gilbert CA, Li L, Daou M, Moser RP, Reeves A, Cochran BH, Ross AH. (2010). Clinically relevant doses of chemotherapy agents reversibly block formation of glioblastoma neurospheres. Biochemistry and Molecular Pharmacology Publications. Retrieved from https://escholarship.umassmed.edu/bmp_pp/125