Wadler S, Wersto R, Weinberg V, Thompson D, Schwartz E L
Department of Oncology, Montefiore Medical Center, Bronx, New York 10467-2490.
Cancer Res. 1990 Sep 15;50(18):5735-9.
Fluorouracil (FUra) is the most active agent in advanced colorectal carcinoma, and this activity can be enhanced by various modulating agents both in vitro and in vivo. To determine whether interferon (IFN) is capable of augmenting the cytotoxic and cytokinetic effects of FUra, combinations of FUra and IFN alpha, -beta, and -gamma were tested against 2 human colon cancer cell lines in vitro. In a clonogenic assay, IFN alpha and -beta, at concentrations that produced less than 1 log cell kill, significantly increased the cytotoxic effects of FUra in both cell lines. IFN gamma also enhanced the cytotoxic effects of FUra, but unlike IFN alpha and -beta, only at the highest concentrations tested. Median effects analysis demonstrated that all 3 IFNs exhibited synergy with FUra. Combinations of IFNs were no more effective at modulating FUra activity than single agent IFN. Flow cytometric studies indicated that these effects did not correlate with cytokinetic alterations. Only the combination of FUra and IFN beta produced cytokinetic effects different from those of FUra alone. Incubation with IFN alpha or IFN gamma for 24 h resulted in only modest cytokinetic alterations, and they did not modify the effects of FUra. These results indicate that IFN is capable of increasing the cytotoxic actions of FUra and that this is separable from any cytokinetic effects produced by the interferons.
氟尿嘧啶（FUra）是晚期结直肠癌中最具活性的药物，并且在体外和体内，这种活性均可被多种调节剂增强。为了确定干扰素（IFN）是否能够增强FUra的细胞毒性和细胞动力学效应，在体外对FUra与IFNα、-β和-γ的组合进行了针对2种人结肠癌细胞系的测试。在克隆形成试验中，浓度产生不到1个对数级细胞杀伤的IFNα和-β显著增强了两种细胞系中FUra的细胞毒性效应。IFNγ也增强了FUra的细胞毒性效应，但与IFNα和-β不同，仅在测试的最高浓度下如此。中位效应分析表明，所有3种IFN均与FUra表现出协同作用。IFN组合在调节FUra活性方面并不比单药IFN更有效。流式细胞术研究表明，这些效应与细胞动力学改变无关。只有FUra与IFNβ的组合产生了与单独使用FUra不同的细胞动力学效应。用IFNα或IFNγ孵育24小时仅导致适度的细胞动力学改变，并且它们并未改变FUra的效应。这些结果表明，IFN能够增强FUra的细胞毒性作用，并且这与干扰素产生的任何细胞动力学效应是可分离的。
