Pannacciulli I, Ballarino P, Castello G, Arboscello E, Botta M, Tredici S, Lerza R
Department of Medicine, University of Genoa, Italy.
Anticancer Res. 1999 Jan-Feb;19(1A):409-12.
The sequence dependency of the interaction of taxol with other anticancer drugs is of clinical importance, and may be due to pharmacokinetic changes and/or to inherent differences in the sensitivity of target normal or cancer cells. This study presents results on the in vitro interaction of taxol with doxorubicin, cisplatin, etoposide and vinorelbine in alternate sequences on human hemopoietic progenitors (CFU-GM). Peripheral blood mononuclear non adherent cells were exposed to IC50 of Taxol for 24 hours and then, for 1 hour to IC50 of each of the other drugs. In a second set of experiments the reverse sequence was applied. The cell suspension was subsequently cultured to assay the growth of CFU-GM. A strong sequence dependency characterizes the combination taxol-vinorelbine, while for the other combinations the order of sequence appears to have little impact on in vitro toxicity on CFU-GM. Comparing results on CFU-GM with that obtained in vitro with the same combination sequences on cancer cell lines some remarkable differences show up. Studies on a normal human myeloid line may therefore have a place in preclinical evaluation of sequence of anticancer drug combinations.
紫杉醇与其他抗癌药物相互作用的序列依赖性具有临床重要性，这可能归因于药代动力学变化和/或靶正常细胞或癌细胞敏感性的内在差异。本研究展示了紫杉醇与阿霉素、顺铂、依托泊苷和长春瑞滨在人造血祖细胞（CFU-GM）上交替序列的体外相互作用结果。外周血单核非贴壁细胞先暴露于紫杉醇的IC50浓度24小时，然后再暴露于其他每种药物的IC50浓度1小时。在第二组实验中采用相反的序列。随后对细胞悬液进行培养以检测CFU-GM的生长情况。紫杉醇-长春瑞滨组合具有很强的序列依赖性，而对于其他组合，序列顺序似乎对CFU-GM的体外毒性影响很小。将CFU-GM的结果与在癌细胞系上用相同组合序列进行体外实验得到的结果相比较，出现了一些显著差异。因此，对正常人髓系细胞系的研究可能在抗癌药物联合使用序列的临床前评估中占有一席之地。
