Kamada N
Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Hokkaido Igaku Zasshi. 1991 Jan;66(1):16-28.
Interferon (IFN)-alpha, -gamma, and two inhibitors of polyamine biosynthesis (alpha-difluoromethyl ornithine; DFMO and methyl glyoxal bis-guanyl hydrazone; MGBG) inhibited the clonal growth of Raji cells. The combination-treatment using two agents, particularly IFN-alpha and DFMO represented synergistic effects. In order to investigate the mechanism of the synergism between IFNs and inhibitors of polyamine biosynthesis, the concentrations of polyamines and the levels of 2'-5' oligo-adenylate synthetase (2-5 AS) activity in the treated Raji cells were determined. Not only the inhibitors of polyamine biosynthesis, but also IFNs decreased the content of spermidine in the cells. Furthermore, the clonogenic growth-inhibition by IFN-alpha was recovered partially by exogenous spermidine. On the other hand, 2-5AS activity in the cells was elevated to 57 times by the treatment with interferon-alpha and further more, the combinations of IFN and the inhibitors of polyamine biosynthesis induced higher activities of 2-5AS as compared with those by each agent. From these results, it was suggested that the synergistic effects of IFNs in combinations with inhibitors of polyamine biosynthesis on the inhibition of clonal growth of Raji cells were closely associated with the decrease of intracellular polyamine level and the increase of 2-5AS activity in the treated cells.
干扰素（IFN）-α、-γ以及两种多胺生物合成抑制剂（α-二氟甲基鸟氨酸；DFMO和甲基乙二醛双胍腙；MGBG）抑制了Raji细胞的克隆生长。使用两种药物的联合治疗，特别是IFN-α和DFMO表现出协同作用。为了研究IFN与多胺生物合成抑制剂之间协同作用的机制，测定了处理后的Raji细胞中多胺的浓度和2'-5'寡腺苷酸合成酶（2-5AS）的活性水平。不仅多胺生物合成抑制剂，IFN也降低了细胞中精胺的含量。此外，外源性精胺部分恢复了IFN-α对克隆生长的抑制作用。另一方面，用干扰素-α处理后，细胞中的2-5AS活性提高到了57倍，而且与每种药物单独处理相比，IFN与多胺生物合成抑制剂的联合处理诱导了更高的2-5AS活性。从这些结果表明，IFN与多胺生物合成抑制剂联合对Raji细胞克隆生长抑制的协同作用与处理细胞中细胞内多胺水平的降低和2-5AS活性的增加密切相关。
