Enhancement of effects of irradiation by gemcitabine in a glioblastoma cell line and cell line spheroids.
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
Genç
Mine
M
Department of Radiotherapy, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands.
Castro Kreder
Natasja
N
Barten-van Rijbroek
Angelique
A
Stalpers
Lukas J A
LJ
Haveman
Jaap
J
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
D000964:Antimetabolites, Antineoplastic; D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D000093542:Gemcitabine