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-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 from healthy donors. IFN-alpha 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 microM against HT-29 and at 1400 microM against MNC on day 2 of culture. 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 cells 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 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-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.
Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
R
R
De Filippi
S P
SP
Prete
A
A
Giuliani
E
E
Silvi
H
H
Yamaue
C A
CA
Nieroda
J W
JW
Greiner
L
L
De Vecchis
E
E
Bonmassar
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000628:therapy*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004357:Drug Synergism; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007370:Interferon Type I / Q000008:administration & dosage / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D010835:Phytohemagglutinins / Q000494:pharmacology; D011994:Recombinant Proteins; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured / Q000187:drug effects
D007370:Interferon Type I; D010835:Phytohemagglutinins; D011994:Recombinant Proteins; D005472:Fluorouracil