5-Fluorouracil (5-FU) and human recombinant gamma-interferon (gamma-IFN) were found to increase the expression of carcinoembryonic antigen (CEA) in human cancer cells in vitro. In the present study, the antimetabolite was associated with gamma-IFN or folinic acid (FA), a biochemical modulator of cellular metabolism of 5-FU, able to increase its antineoplastic activity. Treatment of two human colon cancer cell lines (HT-29 and WiDr) with 5-FU + gamma-IFN resulted in an increase of CEA expression higher than that obtainable with both agents alone, although no synergistic effects were obtained. This was demonstrated in terms of: (a) mRNA transcripts (HT-29); (b) cytoplasm and membrane CEA protein levels detected by Western blot analysis (HT-29); and (c) plasma membrane reactivity determined by flow cytometry analysis (HT-29 and WiDr). Moreover, 5-FU + gamma-IFN increased HLA class I molecules in the HT-29 cell membrane over that obtainable with gamma-IFN alone. In contrast, both agents did not induce the expression of the costimulatory molecule B7-1. Treatment with FA enhanced the antitumor effect of 5-FU but not its ability to augment CEA expression. This suggests that the FA-sensitive biochemical mechanism of action of 5-FU is not involved in its effect on CEA expression. In vivo studies showed, for the first time, that 5-FU, alone or combined with gamma-IFN, increases the amount of CEA protein over controls, either in cancer cells or in peripheral blood of nude mice bearing HT-29 cells. These results could be of potential diagnostic and/or therapeutic value when CEA protein is the target of humoral or cell-mediated immunity.

Aquino, A., Prete, S., Greiner, J., Giuliani, A., Graziani, G., Turriziani, M., et al. (1998). Effect of the combined treatment with 5-fluorouracil, gamma-interferon or folinic acid on carcinoembryonic antigen expression in colon cancer cells. CLINICAL CANCER RESEARCH, 4(10), 2473-2481.

Effect of the combined treatment with 5-fluorouracil, gamma-interferon or folinic acid on carcinoembryonic antigen expression in colon cancer cells

AQUINO, ANGELO;PRETE, SALVATORE;GRAZIANI, GRAZIA;TURRIZIANI, MARIO;BONMASSAR, ENZO;DE VECCHIS, LIANA
1998-01-01

Abstract

5-Fluorouracil (5-FU) and human recombinant gamma-interferon (gamma-IFN) were found to increase the expression of carcinoembryonic antigen (CEA) in human cancer cells in vitro. In the present study, the antimetabolite was associated with gamma-IFN or folinic acid (FA), a biochemical modulator of cellular metabolism of 5-FU, able to increase its antineoplastic activity. Treatment of two human colon cancer cell lines (HT-29 and WiDr) with 5-FU + gamma-IFN resulted in an increase of CEA expression higher than that obtainable with both agents alone, although no synergistic effects were obtained. This was demonstrated in terms of: (a) mRNA transcripts (HT-29); (b) cytoplasm and membrane CEA protein levels detected by Western blot analysis (HT-29); and (c) plasma membrane reactivity determined by flow cytometry analysis (HT-29 and WiDr). Moreover, 5-FU + gamma-IFN increased HLA class I molecules in the HT-29 cell membrane over that obtainable with gamma-IFN alone. In contrast, both agents did not induce the expression of the costimulatory molecule B7-1. Treatment with FA enhanced the antitumor effect of 5-FU but not its ability to augment CEA expression. This suggests that the FA-sensitive biochemical mechanism of action of 5-FU is not involved in its effect on CEA expression. In vivo studies showed, for the first time, that 5-FU, alone or combined with gamma-IFN, increases the amount of CEA protein over controls, either in cancer cells or in peripheral blood of nude mice bearing HT-29 cells. These results could be of potential diagnostic and/or therapeutic value when CEA protein is the target of humoral or cell-mediated immunity.
1998
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/14 - FARMACOLOGIA
English
Con Impact Factor ISI
HUMAN RECOMBINANT INTERFERONS; MONOCLONAL-ANTIBODY; MESSENGER-RNA; COLORECTAL-CANCER; CARCINOMA-CELLS; NUCLEAR-RNA; IN-VITRO; VACCINE; LINES; GENE
Aquino, A., Prete, S., Greiner, J., Giuliani, A., Graziani, G., Turriziani, M., et al. (1998). Effect of the combined treatment with 5-fluorouracil, gamma-interferon or folinic acid on carcinoembryonic antigen expression in colon cancer cells. CLINICAL CANCER RESEARCH, 4(10), 2473-2481.
Aquino, A; Prete, S; Greiner, J; Giuliani, A; Graziani, G; Turriziani, M; De Filippi, R; Masci, G; Bonmassar, E; DE VECCHIS, L
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/52720
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