Akamatsu K, Endo K, Matsumoto T, Morikawa K, Koizumi M, Mitsui H, Koizumi K
Exploratory Research Laboratories, Chugai Pharmaceutical Co., Ltd., Gotemba, Japan.
Anticancer Res. 1991 Jan-Feb;11(1):151-5.
The antitumor mechanism of (-)-(R)-2- aminomethylpyrrolidine (1.1-cyclobutanedicarboxylato)platinum(II) (DWA2114R) was examined using cultured murine L1210 leukemia cells by estimating its effects on parameters such as proliferation, macromolecular synthesis, morphology and cell cycle progression. Each parameter was estimated in cells concomitantly exposed to the drug for 24-48 hr. More than 0.1 microM of DWA2114R markedly inhibited cell proliferation as well as DNA synthesis, and it decreased in mitotic index in a concentration-dependent manner. One microM of DWA2114R decreased DNA synthesis by 80% in the cells treated for 24 hr, while the inhibition of RNA synthesis was less than 40%. A significant inhibition of protein synthesis was caused only by treatment with a high concentration (100 microM) of the drug. Under complete cytostatic conditions (10 microM of DWA2114R), cell volume markedly increased and about 40% of the total cells were polynucleate. In addition, flow cytometrical analysis revealed that most of these cells were accumulated in the G2/M phase of the cell cycle, and a new peak located in the G2/M phase of tetraploid cells emerged. On the other hand, the cells treated with 100 microM of the drug did not increase in volume and their progress in the cell cycle was almost completely blocked.
通过评估(-)-(R)-2-氨甲基吡咯烷(1,1-环丁烷二羧酸根)铂(II)(DWA2114R)对增殖、大分子合成、形态和细胞周期进程等参数的影响，利用培养的小鼠L1210白血病细胞研究了其抗肿瘤机制。在同时暴露于该药物24至48小时的细胞中对每个参数进行评估。超过0.1微摩尔的DWA2114R显著抑制细胞增殖以及DNA合成，并以浓度依赖的方式降低有丝分裂指数。1微摩尔的DWA2114R使处理24小时的细胞中的DNA合成减少80%，而RNA合成的抑制小于40%。仅用高浓度(100微摩尔)的该药物处理才会导致蛋白质合成受到显著抑制。在完全细胞生长抑制条件下(10微摩尔的DWA2114R)，细胞体积显著增加，约40%的总细胞为多核细胞。此外，流式细胞仪分析显示，这些细胞大多积聚在细胞周期的G2/M期，并且出现了一个位于四倍体细胞G2/M期的新峰。另一方面，用100微摩尔该药物处理的细胞体积没有增加，并且它们在细胞周期中的进程几乎完全受阻。
