Gemcitabine treatment of experimental C6 glioma: the effects on cell cycle and apoptotic rate.
Gemcitabine (dFdCyd) is a deoxycytidine analogue showing a broad spectrum of cytotoxic activity; additionally, at non-cytotoxic concentrations, it is a potent radiosensitiser. Its in vitro and in vivo effects were studied on C6 rat glioma. In vitro, dFdCyd induced an increase in S-phase cells at the end of treatment, with a reduction in G1 and G2 cell cycle-phase cells and relevant effects on the apoptotic rate. The in vivo effects of dFdCyd were studied on rats bearing intracranial C6 glioma. The drug was administered at a dose of 120 mg/Kg every 3 days x 4 doses. A significant effect on tumour growth was detected by longitudinal MRI analyses. Furthermore, the drug induced an inhibitory effect on tumour growth, 72 h after a 300 mg/Kg single dose. Analyses performed on tumour specimens showed relevant G1-phase accumulation and about 45% apoptotic cells. The present results justify further studies to determine the potential efficacy of dFdCyd in the treatment of malignant gliomas.
Carpinelli
Giulia
G
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome, Italy. carapella@ifo.it
Bucci
Barbara
B
D'Agnano
Igea
I
Canese
Rossella
R
Caroli
Fabrizio
F
Raus
Laura
L
Brunetti
Ercole
E
Giannarelli
Diana
D
Podo
Franca
F
Carapella
Carmine M
CM
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine