DIFFERENTIAL-EFFECTS OF RECOMBINANT INTERFERON-ALPHA AND 5-FLUOROURACIL AGAINST COLON-CANCER CELLS OR AGAINST PERIPHERAL-BLOOD MONONUCLEAR-CELLS

Comparative studies on the suppressive effects of recombinant interfer on-alpha (IFN-alpha), 5-fluorouracil (5-FU), or IFN-alpha + 5-FU have been performed in vitro on colon carcinoma cells (HT-29 cell line) and PHA-stimulated mononuclear cells (MNC) of peripheral blood obtained f rom healthy donors. IFN-alpha was used at 500 U/ml against HT-29 cells and at 1000 U/ml against MNC on day I of culture; 5-FU was used cat 2 50 mu M against HT-29 find at 1400 mu M against MNC on day 2 of cultur e. The results show that: (a) IFN-alpha inhibited MNC and HT-29 cells by 13.4% and 32.9%, respectively; (b) 5-FU inhibited MNC and HT-29 cel ls by 54.7% and 87.0%, respectively; (c) IFN-alpha + 5-FU resulted in. a stronger inhibition of HT-29 cells (i.e., 96.1%). In contrast, that combination was significantly less suppressive than 5-FU alone when M NC were used as targets (i.e., 35.9% inhibition). Natural cell-mediate d cytotoxic activity relative to 10(6) MNC was not markedly altered by all agents alone or in combination Moreover, treatment with IFN-alpha , 5-FU or IFN-alpha + 5-FU resulted in a marked increase in the number of HT-29 cells positive for the CEA surface antigen. These data seem to provide further rational support of the clinical use of IFN-alpha 5-FU in colorectal cancer, based on the differential toxicity of this drug combination on tumor versus normal immunocompetent cells.