The anti-tumour effects of the prodrugs N-l-leucyl-doxorubicin and vinblastine-isoleucinate in human ovarian cancer xenografts.
The anti-tumour effects of the prodrugs N-l-leucyl-doxorubicin and vinblastine-isoleucinate in human ovarian cancer xenografts.
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DOI：
10.1038/bjc.1992.407
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发表时间：
1992-12
影响因子：
8.8
通讯作者：
Pinedo, H M
中科院分区：
文献类型：
--
作者：
Boven, E;Hendriks, H R;Erkelens, C A;Pinedo, H M
N-L-亮氨酰-阿霉素和长春花碱-异亮氨酸分别是阿霉素和长春花碱的相对无毒前药。对四种不同组织学、生长速度和化疗敏感性的人卵巢癌移植瘤与长春新碱进行了抗肿瘤活性的比较分析。静脉注射。每周两次注射给体内发育良好的S.C.小鼠。肿瘤。在等毒剂量下，N-L-亮氨酰阿霉素和长春花碱-异亮氨酸的给药量分别是母体的3倍和2倍。N-L-亮氨酰-阿霉素对四种人卵巢癌细胞株中的三种有抑制作用，抑制率为50%。抗肿瘤效果明显优于阿霉素(P<；0.01)。在其中两个品系中研究的长春花碱-异亮酸可以诱导50%的生长抑制。这种前药的效果似乎略逊于长春花碱。长春新碱对肿瘤细胞的生长抑制作用不明显，抑制率为50%。
N-l-leucyl-doxorubicin and vinblastine-isoleucinate can be considered as relatively non-toxic prodrugs from doxorubicin and vinblastine, respectively. A comparative analysis was carried out of the anti-tumour activity of the four compounds as well as vintriptol in four human ovarian cancer xenografts different in histology, growth rate and chemosensitivity. Injections were given i.v. weekly twice into mice bearing well-established s.c. tumours. At equitoxic doses, the amount of drug administered for N-l-leucyl-doxorubicin and vinblastine-isoleucinate was respectively 3-fold and 2-fold higher than the doses of the parent compound. N-l-leucyl-doxorubicin induced a growth inhibition > 50% in three out of four human ovarian cancer lines. The anti-tumour effects obtained were significantly better (P < 0.01) than in the case of doxorubicin. Vinblastine-isoleucinate studied in two of these lines could induce a growth inhibition of > 50%. This prodrug appeared slightly less effective than vinblastine. Insignificant growth inhibition (< 50%) was obtained by vintriptol.