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
✍ Scribed by Ingrid W. H. M. Maas; Epie Boven; Herbert M. Pinedo; Hennie M. M. Schlüper; Hidde J. Haisma
- Publisher
- John Wiley and Sons
- Year
- 1991
- Tongue
- French
- Weight
- 840 KB
- Volume
- 48
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Gamma-Interferon (IFN-y) and the antimetabolites 5fluorouracil(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-I antigen, carcinoembryonic antigen (CEA) and the intracellular tumor-associated antigen CTA-I in 7 human colorectal cancer cell lines: WiDr, HT29. Colo 205, SW I I 16, LS I74T. SW 1398, and LoVo. Growth inhibition by I F N y at clinically relevant concentrations (SCrlOO Ulml) was found in 4/7 cell lines. The cell lines were equally sensitive to 5-FU (IC, in a range of 2-10 p ~) , while sensitivity t o FUdR varied considerably (lCs0 in a range of 0.01-90 p ~) .
When 50 Ulml IFN-y were combined with 5-FU or FUdR, the antiproliferative effects were synergistic in those cell lines with sensitivity t o IFN-y as a single agent, b u t n o t i n the IFN-y-insensitive cell lines. IFN-y was able to enhance the expression of H L A Class I and CEA in 4/7 and 3/7 cell lines, respectively, as measured by flow cytometry. CTA-I expression could not be enhanced with IFN-y. 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 Ulml IFN-y 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-y or the anti-metabolites. The enhancement in antigen expression also did not show a relationship with changes in cell-cycle distribution upon exposure t o IFN-y or the anti-metabolites. These results suggest independent mechanisms for the antiproliferative and antigen-enhancing effects of