Lopez Ballester J A, Peñafiel R, Cremades A, Valcarcel M M, Solano F, Lozano J A
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Murcia, Spain.
Anticancer Res. 1991 Mar-Apr;11(2):691-6.
The oral administration of alpha-difluoromethylornithine (DFMO), an enzyme-activated inhibitor of ornithine decarboxylase (ODC), produced a marked decrease in the rate of growth of amelanotic Harding-Passey melanoma transplanted in mice. The half-life of this compound in Harding-Pasey melanoma was 30 min. A combined treatment of DFMO and hyperthermia did not show any synergistic effect on the inhibition of tumor growth, and no differences in the levels of tumor ODC, S-Adenosylmethionine decarboxylase (SAMDC) and polyamines were observed between single and combination treatments. DFMO-treatment alone produced a decrease of about 80% in spermidine concentration in melanoma, while in other tissues such as kidney, the diminution of spermidine was only moderate. ODC activity was reduced greatly in the kidney and moderately in melanoma. However, the activity of SAMDC increased up to 30-fold in DFMO-treated melanoma, while only a moderate increase was observed in the renal enzyme. Melanoma tyrosinase activity did not increase with the treatment with DFMO. These results indicate that the inhibition of amelanotic Harding-Passey melanoma growth by DFMO is not caused by the stimulation of cell differentiation, and that in this system polyamine depletion caused by this drug does not produce an enhancement in the heat-induced cytotoxicity.
口服α-二氟甲基鸟氨酸（DFMO），一种鸟氨酸脱羧酶（ODC）的酶激活抑制剂，可显著降低移植到小鼠体内的无黑色素哈丁-帕西黑色素瘤的生长速度。该化合物在哈丁-帕西黑色素瘤中的半衰期为30分钟。DFMO与热疗联合治疗对肿瘤生长抑制未显示出任何协同作用，单药治疗与联合治疗之间在肿瘤ODC、S-腺苷甲硫氨酸脱羧酶（SAMDC）和多胺水平上未观察到差异。单独使用DFMO治疗可使黑色素瘤中的亚精胺浓度降低约80%，而在肾脏等其他组织中，亚精胺的减少仅为中等程度。ODC活性在肾脏中大幅降低，在黑色素瘤中适度降低。然而，在DFMO治疗的黑色素瘤中，SAMDC活性增加高达30倍，而在肾脏酶中仅观察到适度增加。DFMO治疗后黑色素瘤酪氨酸酶活性未增加。这些结果表明，DFMO对无黑色素哈丁-帕西黑色素瘤生长的抑制不是由细胞分化的刺激引起的，并且在该系统中，该药物引起的多胺耗竭不会增强热诱导的细胞毒性。
