Interaction of Fluorouracil and Interferon in Human Colon Cancer Cell Lines: Cytotoxic and Cytokinetic Effects

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 IFNα, β, and -γ were tested against 2 human colon cancer cell lines in vitro. In a clonogenic assay, IFNa and -0, at concentrations that produced less than 1 log cell kill, significantly increased the cytotoxic effects of FUra in both cell lines. IFN7 also enhanced the cytotoxic effects of FUra, but unlike IFNa and -0, 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 IFN0 produced cytokinetic effects different from those of FUra alone. Incubation with IFNa or IFN7 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.