Anehus S, Oredsson S M, Heby O
Department of Zoophysiology, University of Lund, Sweden.
Cell Biochem Funct. 1988 Apr;6(2):115-21. doi: 10.1002/cbf.290060206.
When Ehrlich ascites tumour cells are induced to proliferate by serum stimulation, the ornithine decarboxylase (ODC) activity increases rapidly and reaches two to three peaks during the first 24 h. Inhibition of the first peak in ODC activity (occurring at 4 h) by adding alpha-difluoromethylornithine (DFMO) within 2 h of serum stimulation, results in maximal growth inhibition. Under these conditions, similar degrees of polyamine depletion are achieved. When DFMO is added 3 h after seeding, however, enough polyamines have already accumulated during the initial burst in ODC activity to reduce the antiproliferative effect of the drug. The antiproliferative effect is further reduced when DFMO is added 6 h after seeding. When DFMO is added 23 h after seeding, i.e. after maximal accumulation of polyamines, there is no inhibition of cell proliferation. These findings are important to consider both when designing experimental as well as clinical regimens for this drug.
当通过血清刺激诱导艾氏腹水瘤细胞增殖时，鸟氨酸脱羧酶（ODC）活性迅速增加，并在最初的24小时内达到两到三个峰值。在血清刺激后2小时内添加α-二氟甲基鸟氨酸（DFMO）抑制ODC活性的第一个峰值（在4小时出现），会导致最大程度的生长抑制。在这些条件下，可实现相似程度的多胺耗竭。然而，当在接种后3小时添加DFMO时，在ODC活性最初的爆发期间已经积累了足够的多胺，从而降低了该药物的抗增殖作用。当在接种后6小时添加DFMO时，抗增殖作用进一步降低。当在接种后23小时添加DFMO时，即在多胺最大积累之后，没有细胞增殖抑制作用。在设计该药物的实验方案和临床方案时，这些发现都很重要，需要加以考虑。
