Rantapää Dahlqvist S, Landberg G, Roos G, Norberg B
Department of Rheumatology, University Hospital, Umeå, Sweden.
Br J Rheumatol. 1994 Apr;33(4):327-31. doi: 10.1093/rheumatology/33.4.327.
The benzylidated podophyllotoxin glycoside CPH82, a potentially useful drug for treatment of RA, was tested in vitro on nine human haematopoietic cell lines for cell kinetic effects. Previous studies have shown CPH82 to behave like a colchine-type 'metaphase' blocker. The distribution of cells within different cell cycle compartments (G1, S, G2 and M) was analysed by a novel method using dual parameter flow cytometric analysis of stage specific antigens (proliferating cell nuclear antigen and Ki-67). With CPH82 concentrations chosen to mimic clinical conditions, eight out of nine lines showed an accumulation of cells in the G2 phase of the cell cycle. In many lines a delayed progress through S seemed to occur. Three lines were blocked in both G1 and G2, whereas the major effect on one line (HL-60) was an accumulation of cells in the G1 phase. Progression of M cells seemed only slightly delayed for some cell lines. In comparison with two related 'metaphase' blocking agents (podophyllotoxin and taxol), CPH82 had a different and dose-dependent pattern of cell cycle retardation. It is speculated that the cell kinetic action of CPH82 might give insight into the question why it, unlike other 'metaphase' blockers, has proved valuable in the treatment of RA.
苄基化鬼臼毒素糖苷CPH82是一种可能对类风湿性关节炎治疗有用的药物，在体外对九种人类造血细胞系进行了细胞动力学效应测试。先前的研究表明CPH82表现得像一种秋水仙碱型的“中期”阻断剂。使用阶段特异性抗原（增殖细胞核抗原和Ki-67）的双参数流式细胞术分析的新方法，分析了不同细胞周期区室（G1、S、G2和M）内的细胞分布。选择模拟临床条件的CPH82浓度，九条细胞系中有八条显示细胞在细胞周期的G2期积累。在许多细胞系中，似乎出现了S期进展延迟。三条细胞系在G1和G2期均被阻断，而对一条细胞系（HL-60）的主要影响是细胞在G1期积累。对于一些细胞系，M期细胞的进展似乎仅略有延迟。与两种相关的“中期”阻断剂（鬼臼毒素和紫杉醇）相比，CPH82具有不同的且剂量依赖性的细胞周期阻滞模式。据推测，CPH82的细胞动力学作用可能有助于深入了解为什么与其他“中期”阻断剂不同，它在类风湿性关节炎治疗中已被证明具有价值这一问题。
