INTERACTION OF FLUOROURACIL AND INTERFERON IN HUMAN COLON CANCER CELL-LINES - CYTOTOXIC AND CYTOKINETIC EFFECTS

  • 15 September 1990
    • journal article
    • research article
    • Vol. 50  (18) , 5735-5739
Abstract
Fluorouracil (FUra) is the most active agent in advanced colorectal carcinoma, and this activity can be enhanced by various modulating agents both by 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. Combination 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.