title: Enhancement of effects of irradiation by gemcitabine in a glioblastoma cell line and cell line spheroids.
abstract: OBJECTIVE
  To determine the cytotoxicity of, and radioenhancement by, gemcitabine on a glioma cell line grown as a monolayer and as spheroid cultures.
  
  
  METHODS
  We used a human glioma cell line, Gli-6, which originated from a biopsy specimen of a patient with a glioblastoma multiforme. Spheroids of Gli-6 were prepared by seeding a single cell suspension on agarose-coated Petri dishes. Clonogenic and growth delay assays were used to determine radio-chemosensitivity of monolayer cultures. The growth delay assay was used to determine that of Gli-6 spheroid cultures.
  
  
  RESULTS
  Spheroid cultures were found to be more resistant to irradiation with/or without gemcitabine than monolayer cultures. Whereas gemcitabine significantly enhances the radiation effect of exponentially growing Gli-6 monolayer cultures at minimal cytotoxic concentrations (10 nM, 24 h), no enhancement was seen in confluent monolayer cultures and in large spheroids at the same concentration. In small spheroids no enhancement was observed at a low-dose gemcitabine (10 nM for 24 h), but an enhancement was observed at higher concentrations (100 nM for 24 h).
  
  
  CONCLUSIONS
  Gemcitabine can lead to enhancement of the effects of X-irradiation in both monolayer as spheroid glioblastoma cultures. The lack of enhancement in confluent monolayer cultures supports the view that cell cycle distribution of cells is important in radiosensitisation by gemcitabine
authors: Department of Radiotherapy, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands.
authors: Mine
authors: M
authors: Genç
authors: Natasja
authors: N
authors: Castro Kreder
authors: Angelique
authors: A
authors: Barten-van Rijbroek
authors: Lukas J A
authors: LJ
authors: Stalpers
authors: Jaap
authors: J
authors: Haveman
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005909:Glioblastoma / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D018874:Spheroids, Cellular; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D000093542:Gemcitabine