α-Difluoromethylornithine Increases the Anti-tumor Effect of cis-Diamminedichloroplatinum in G-XII Rat Glioma

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The in vivo effects of the single or combined administration of α-difluoromethylornithine (DFMO), an inhibitor of polyamine synthesis, and cis-diamminedichloroplatinum (cisplatin) on the growth of GXII 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.