Murata K, Sato T, Kanamaru R
Dept. of Clinical Oncology, Tohoku University.
Gan To Kagaku Ryoho. 1994 Feb;21(3):307-13.
The antitumor effect of a new derivative of taxol, docetaxel (RP56976), was examined in K562 human tumor system in vitro. K562 cells presenting a multidrug resistant phenotype showed cross resistance to docetaxel. However, the resistance levels of docetaxel in these cell lines were much lower than for adriamycin and vincristine. Flow cytometric analysis showed the accumulation of cells into G2/M phase after 18hrs. Wright-Giemsa staining showed a marked increase of metaphase population. Docetaxel was shown to promote the assembly of microtubule protein without GTP in vitro, but no inhibitory effect on DNA, RNA and protein synthesis. Moreover, topoisomerase activities were not affected by docetaxel. These results indicate that docetaxel acts as a strong mitotic inhibitor in cancer chemotherapy.
在体外K562人肿瘤系统中检测了一种新的紫杉醇衍生物多西他赛(RP56976)的抗肿瘤作用。呈现多药耐药表型的K562细胞对多西他赛表现出交叉耐药性。然而,这些细胞系中多西他赛的耐药水平远低于阿霉素和长春新碱。流式细胞术分析显示,18小时后细胞积累进入G2/M期。瑞氏-吉姆萨染色显示中期细胞群体显著增加。多西他赛在体外可促进无GTP的微管蛋白组装,但对DNA、RNA和蛋白质合成无抑制作用。此外,多西他赛不影响拓扑异构酶活性。这些结果表明,多西他赛在癌症化疗中起强效有丝分裂抑制剂的作用。