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The effects of γ‐interferon combined with 5‐fluorouracil or 5‐fluoro‐2′‐deoxyuridine on proliferation and antigen expression in a panel of human colorectal cancer cell lines
Author(s) -
Maas Ingrid W. H. M.,
Boven Epie,
Pinedo Herbert M.,
Schlüper Hennie M. M.,
Haisma Hidde J.
Publication year - 1991
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910480520
Subject(s) - carcinoembryonic antigen , cell culture , antigen , flow cytometry , cell growth , microbiology and biotechnology , human leukocyte antigen , cancer research , biology , chemistry , medicine , immunology , cancer , biochemistry , genetics
Gamma‐lnterferon (IFN‐γ) and the antimetabolites 5‐fluorouracil (5‐FU) and 5‐fluoro‐2′‐deoxyuridine (FUdR) were investigated as individual agents and in combination for their In vitro antiproliferative capacity and for their effect on the expression of HLA class‐1 antigen, carcinoembryonic antigen (CEA) and the intracellular tumor‐associated antigen CTA‐I In 7 human colorectal cancer cell lines: WiDr, HT29, Colo 205, SW1116, LS174T, SW1398, and LoVo. Growth inhibition by IFN‐γ at clinically relevant concentrations (50–100 U/ml) was found in 4/7 cell lines. The cell lines were equally sensitive to 5‐FU (IC 50 , in a range of 2–10 μM), while sensitivity to FUdR varied considerably (IC 50 in a range of 0.01–90 μM). When 50 U/ml IFN‐γ were combined with 5‐FU or FUdR, the antiproliferative effects were synergistic in those cell lines with sensitivity to IFN‐γ as a single agent, but not in the IFN‐γ‐insensitive cell lines. IFN‐γ was able to enhance the expression of HLA Class I and CEA in 4/7 and 3/7 cell lines, respectively, as measured by flow cytometry. CTA‐1 expression could not be enhanced with IFN‐γ. The expression of the 3 antigens tested was also increased by 5‐FU and FUdR. This effect was concentration‐dependent in most instances and varied between the individual cell lines. The combination of 50 U/ml IFN‐γ with 25% growth‐inhibitory concentration of 5‐FU or FUdR for each cell line resulted in an additional increase in antigen expression in 4/7 cell lines. No relation was found between the enhancement of antigen expression and the sensitivity to IFN‐γ or the anti‐metabolites. The enhancement in antigen expression also did not show a relationship with changes in cell‐cycle distribution upon exposure to IFN‐γ or the anti‐metabolites. These results suggest independent mechanisms for the antiproliferative and antigen‐enhancing effects of IFN‐γ, 5‐FU and FUdR.