alpha-Difluoromethylornithine increases the anti-tumor effect of cis-diamminedichloroplatinum in G-XII rat glioma.
The in vivo effects of the single or combined administration of alpha-difluoromethylornithine (DFMO), an inhibitor of polyamine synthesis, and cis-diamminedichloroplatinum (cisplatin) on the growth of G-XII glioma cells inoculated subcutaneously in rats were tested. Treatment with DFMO or cisplatin significantly decreased the bromodeoxyuridine (BrdU) labeling index of tumor tissues. Combined treatment with DFMO and cisplatin achieved a further significant decrease in the BrdU labeling index. All treatments significantly reduced the tissue levels of N1-acetylspermidine and putrescine, and the ornithine decarboxylase (ODC) activity, but little affected the tissue levels of spermidine and spermine, and the activity of spermidine/spermine N1-acetyltransferase. The reduction of ODC activity by cisplatin treatment may be associated with the anti-tumor effect.
Kurihara
H
H
Department of Neurosurgery, Gunma University School of Medicine, Maebashi.
Matsuzaki
S
S
Tamura
M
M
Sugimoto
H
H
Tsukahara
T
T
Yamazaki
H
H
D000123:Acetyltransferases / Q000032:analysis / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D001973:Bromodeoxyuridine / Q000032:analysis / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D046508:Culture Techniques; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D000518:Eflornithine / Q000494:pharmacology* / Q000627:therapeutic use*; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology*; D009955:Ornithine Decarboxylase / Q000032:analysis / Q000378:metabolism; D051381:Rats
D000123:Acetyltransferases; D009955:Ornithine Decarboxylase; D001973:Bromodeoxyuridine; D002945:Cisplatin; D000518:Eflornithine