Supraadditive effect of 2′,2′-difluorodeoxycytidine (gemcitabine) in combination with oxaliplatin in human cancer cell lines
Supraadditive effect of 2′,2′-difluorodeoxycytidine (gemcitabine) in combination with oxaliplatin in human cancer cell lines
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DOI：
10.1007/s002800050955
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发表时间：
1999-08-01
影响因子：
3
通讯作者：
Cvitkovic, E
中科院分区：
文献类型：
--
作者：
Faivre, S;Raymond, E;Cvitkovic, E
目的：本研究评估了核苷类似物吉西他滨联合二氨基环己烷铂化合物奥沙利铂的细胞毒性作用。方法：采用人CEM白血病细胞系和结肠癌细胞系HCT 116和科尔320 DM进行生长抑制研究。使用相似的实验设置，在相同的细胞系中比较吉西他滨-奥沙利铂组合与吉西他滨-顺铂组合。将细胞暴露于吉西他滨2小时，然后暴露于奥沙利铂或顺铂24小时，反之亦然。结果如下：50%抑制浓度在使用暴露于吉西他滨2小时和暴露于奥沙利铂或顺铂24小时的单药实验中，CEM细胞的IC 50值分别为89 pM、11.1 μ M和10.3 μ M; HCT 116细胞的IC 50值分别为46 pM、10.2 μ M和2.7 μ M;而对于科洛320 DM细胞为102 pM、4.6 μ M和8.6 μ M。吉西他滨-奥沙利铂联合用药在人白血病和结肠癌细胞系中显示出超累加效应。在HCT 116和科尔320 DM结肠癌细胞系中，吉西他滨+奥沙利铂的顺序比相反顺序更有效。而奥沙利铂随后吉西他滨的顺序在CEM细胞中产生协同效应。吉西他滨-奥沙利铂组合的细胞毒性作用优于（HCT 116细胞）或等于（CEM和科尔320 DM细胞）吉西他滨-顺铂组合的细胞毒性作用。结论：我们的数据表明，吉西他滨与奥沙利铂的组合在人白血病和结肠癌细胞中发挥了有效的抗增殖作用，在I-II期试验的框架内进一步研究作为治疗实体恶性肿瘤的替代方案。
Purpose: This study assessed the cytotoxic effects of the nucleoside analog gemcitabine in combination with the diaminocyclohexane platinum compound oxaliplatin. Methods: Growth inhibition studies were performed using the human CEM leukemia cell line and the colon-cancer cell lines HCT 116 and Cole 320 DM. Gemcitabine-oxaliplatin combinations were compared with gemcitabine-cisplatin combinations in the same cell lines using similar experimental settings. Cells were exposed for 2 h to gemcitabine and then for 24 h to oxaliplatin or cisplatin, and vice versa. Results: The 50% inhibitory concentrations (IC50 values) in single-drug experiments using 2 h of exposure to gemcitabine and 24 h of exposure to oxaliplatin or cisplatin were, respectively, 89 pM, 11.1 mu M, and 10.3 mu M for CEM cells; 46 pM, 10.2 mu M, and 2.7 mu M for HCT 116 cells; and 102 pM, 4.6 mu M, and 8.6 mu M for Colo 320 DM cells. Gemcitabine-oxaliplatin combinations displayed supraadditive effects in human leukemia and colon-cancer cell lines. The sequence of gemcitabine followed by oxaliplatin was more effective than the opposite sequence in HCT 116 and Cole 320 DM colon-cancer cell lines. whereas the sequence of oxaliplatin followed by gemcitabine yielded to synergistic effects in CEM cells. The cytotoxic effects of gemcitabine-oxaliplatin combinations were better than (HCT 116 cells) or equal to (CEM and Cole 320 DM cells) those of gemcitabine-cisplatin combinations. Conclusion: Our data show that the combination of gemcitabine with oxaliplatin exerts potent antiproliferative effects in human leukemia and colon cancer cells, warranting further investigations in the framework of phase I-II trials as an alternative for the treatment of solid malignancies.