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

Cancer Lett. 2010 Oct 28;296(2):168-77. doi: 10.1016/j.canlet.2010.04.005.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Carmustine / therapeutic use
  • Cell Adhesion
  • Cell Culture Techniques
  • Cell Death
  • Cell Division
  • Cell Line, Tumor
  • DNA Primers
  • DNA, Complementary / genetics
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / therapeutic use
  • Exons
  • Glioblastoma / drug therapy*
  • Glioblastoma / pathology
  • Glioblastoma / physiopathology
  • Glioblastoma / radiotherapy
  • Glioblastoma / surgery
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Recurrence, Local
  • Prognosis
  • Temozolomide
  • Transplantation, Heterologous
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Antineoplastic Agents, Alkylating
  • DNA Primers
  • DNA, Complementary
  • Dacarbazine
  • Carmustine
  • Temozolomide