Takamoto S, Ota K
Gan To Kagaku Ryoho. 1986 May;13(5):1868-75.
THP-adriamycin (THP) is a new derivative of adriamycin (ADM) which is reported to have a lower cardiotoxicity than ADM. In this report, the effects of THP on cell growth, cell cycle traverse and colony-forming ability of RPMI-8402 cells were investigated in comparison with ADM. The growth-inhibitory effect of THP was equal or superior to that of ADM in this system. Analysis of the DNA histogram obtained by flow cytometry showed that THP exerted its growth-inhibitory effect by blocking cells at the G2 phase. At higher concentrations, THP inhibited the traverse of cells through the S phase and further through the whole cell cycle completely. These effects were quite similar to those of ADM, which suggested a similar mechanism of action for the two drugs from the aspect of the cell cycle. A follow-up study of cells accumulated at the G2 phase and a study on colony-forming ability revealed that the G2 phase accumulation was an irreversible and fatal effect of THP, so that G2-phase accumulation could be considered as a cytocidal effect of THP, indicating the clinical usefulness of this system for evaluation of the drug effect. From these results and the low cardiotoxicity, it was suggested that THP could be a good candidate for use as an antitumor agent in clinics.
吡柔比星（THP）是阿霉素（ADM）的一种新衍生物，据报道其心脏毒性低于ADM。在本报告中，将THP与ADM进行比较，研究了THP对RPMI-8402细胞的细胞生长、细胞周期进程和集落形成能力的影响。在该系统中，THP的生长抑制作用与ADM相当或优于ADM。通过流式细胞术获得的DNA直方图分析表明，THP通过将细胞阻滞在G2期发挥其生长抑制作用。在较高浓度下，THP抑制细胞通过S期并进一步完全通过整个细胞周期。这些作用与ADM的作用非常相似，这从细胞周期方面提示了两种药物的作用机制相似。对阻滞在G2期的细胞进行的后续研究以及对集落形成能力的研究表明，G2期阻滞是THP的一种不可逆的致死性作用，因此G2期阻滞可被视为THP的一种杀细胞作用，这表明该系统在评估药物疗效方面具有临床实用性。从这些结果以及低心脏毒性来看，提示THP可能是临床上一种很好的抗肿瘤药物候选物。
