Synergism of the polyamine analogue, N-1,N-11-bisethylnorspermine with cis-diaminedichloroplatinum(II) against murine neoplastic cell lines in vitro and in vivo
Synergism of the polyamine analogue, N-1,N-11-bisethylnorspermine with cis-diaminedichloroplatinum(II) against murine neoplastic cell lines in vitro and in vivo
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DOI：
10.1016/0304-3835(95)04043-9
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发表时间：
1996-01-19
期刊：
影响因子：
9.7
通讯作者：
Austin, JK
中科院分区：
文献类型：
--
作者：
Hawthorne, TR;Austin, JK
利用天然存在的多胺的活性来增强顺铂的抗肿瘤活性。多胺类似物 N-1,N-11-双乙基去甲精胺 (BE-3-3-3) 在 L1210 白血病悬浮培养物和 B16 F1 黑色素瘤细胞的铺板效率测定中以亚治疗水平使用，可分别将顺铂的细胞毒性作用提高七倍和十倍。在小鼠中进行的类似实验揭示了优化组合比例后，对携带 L1210 的 DBA/2J 小鼠具有累加效应，对携带 B16 F-1 肿瘤的 C57/B6 小鼠具有协同效应。在后一种模型中，BE-3-3-3/顺铂摩尔比为 250:1 时，在 9 天的给药方案中记录到寿命 (ILS) 增加了 56%，而相同剂量的 BE-3-3-3 导致了 21% ILS，而顺铂仅表现出 7% ILS。讨论了体外和体内活性差异的可能原因。
The activities of naturally occurring polyamines are exploited to enhance the antitumor activity of cisplatin. The polyamine analogue, N-1,N-11-bis-ethylnorspermine (BE-3-3-3) is used at subtherapeutic levels in L1210 leukemia suspension cultures and plating efficiency assays of B16 F1 melanoma cells to increase the cytotoxic effect of cisplatin seven- and tenfold, respectively. Similar experiments in mice reveal additive effects for DBA/2J mice bearing L1210 and synergistic effects in C57/B6 mice bearing B16 F-1 tumor after optimizing combination ratios. In the latter model, at a BE-3-3-3/cisplatin molar ratio of 250:1, an increased lifespan (ILS) of 56% is recorded during a 9-day dosing schedule, whereas BE-3-3-3 at the same dose caused a 21% ILS, and cisplatin only exhibited a 7% ILS. Possible reasons for differences between in vitro and in vivo activity are discussed.