Yokomori K, Tsuchida Y, Saito S, Yamamoto H, Takakura K, Nomura K
Gan. 1983 Dec;74(6):902-10.
The effects of cis-dichlorodiammineplatinum (CDDP) on the cell kinetics of human neuroblastoma both in vitro and in vivo were analyzed by computer-aided flow cytometry. In the in vitro system, CDDP at the concentration of 1.0 microgram/ml of medium blocked early S phase and synchronized proliferating cells into the S phase within 24 hr. By 72 hr, cells in G2 + M phase reached the maximum level. CDDP at concentrations either lower or higher than 1.0 microgram/ml showed no synchronization effect. In the in vivo system, human neuroblastoma grown in nude mice had a larger proportion of cells in G0 + G1 phase than did in vitro cells of the same origin, explaining the refractory nature of the tumors to therapy. CDDP, when given as a single dose of 10 mg/kg of mouse weight showed a maximum synchronization of cells in the S phase by 48 hr, and caused an accumulation of cells in G2 + M phase by 72 hr. This accumulation of cells in G2 + M phase was thought to represent the overflow of cells from the S phase into G2 + M phase, resulting from the disappearance of the blocking effect of CDDP with time. Judging from these sequential changes in vivo, a second drug with specific cytocidal effect on S phase cells should work best 48 hr after the initial CDDP therapy, and drugs specific to G2 + M phase or radiotherapy should be added at 72 hr. Such preclinical experiments may be useful in the design of combination chemotherapy regimens against human neuroblastoma.
通过计算机辅助流式细胞术分析了顺二氯二氨铂（CDDP）对人神经母细胞瘤细胞动力学的体内外作用。在体外系统中，培养基中浓度为1.0微克/毫升的CDDP阻断早期S期，并在24小时内将增殖细胞同步到S期。到72小时时，G2+M期细胞达到最高水平。浓度低于或高于1.0微克/毫升的CDDP均未显示同步化作用。在体内系统中，裸鼠体内生长的人神经母细胞瘤中处于G0+G1期的细胞比例比相同来源的体外细胞更大，这解释了肿瘤对治疗的难治性。当以10毫克/千克小鼠体重的单剂量给予CDDP时，48小时时S期细胞同步化程度最高，72小时时导致细胞在G2+M期积累。G2+M期细胞的这种积累被认为代表了随着时间推移CDDP阻断作用消失，细胞从S期溢流到G2+M期。从体内这些连续变化来看，对S期细胞具有特异性杀伤作用的第二种药物应在初始CDDP治疗后48小时使用效果最佳，而对G2+M期具有特异性的药物或放疗应在72小时添加。此类临床前实验可能有助于设计针对人神经母细胞瘤的联合化疗方案。
