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 interferon-alpha (IFN-α), 5-fluorouracil (5-FU), or IFN-α + 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 from healthy donors. IFN-α was used at 500 U/ml against HT-29 cells and at 1000 U/ml against MNC on day 1 of culture; 5-FU was used at 250 μM against HT-29 and at 1400 μM against MNC on day 2 of culture. The results show that: (a) IFN-α inhibited MNC and HT-29 cells by 13.4% and 32.9% respectively; (b) 5-FU inhibited MNC and HT-29 cells by 54.7% and 87.0% respectively; (c) IFN-α+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 MNC were used as targets (i.e., 35.9% inhibition). Natural cell-mediated cytotoxic activity relative to 10 6 MNC was not markedly altered by all agents alone or in combination. Moreover, treatment with IFN-α, 5-FU or IFN-α + 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-α + 5-FU in colorectal cancer, based on the differential toxicity of this drug combination on tumor versus normal immunocompetent cells