Abstract
In sera of cachectic patients bearing advanced cancers, the concentration of interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrotizing factor-α (TNF-α), and interferon-γ (IFN-γ) have been reported to elevate. In this study, we investigated whether those cytokines influenced in vitro anti-tumor effect of 5-fluorouracil (5-FU) on a human colon tumor cell line, HCT-15. Pretreatment of HCT-15 cells with IL-1 β, IL-6 or TNF-α did not affect the anti-tumor effect of 5-FU at various concentrations. However, IFN-γ attenuated the anti-tumor effect of 5-FU at the concentrations of 0.1–10 IU/ml. An experiment with tritium thymidine showed that 0.1 IU/ml of IFN-γ did not suppress the growth of HCT-15 cells. As low as 0.1 IU/ml of IFN-γ attenuated the anti-tumor effect of 5-FU in another experimental system where HCT-15 cells were exposed to 0.1 IU/ml of IFN-γ before and during the treatment with 5-FU. This system mimicked the clinical condition around in situ cancer cells. Treatment of HCT-15 cells with 0.1–10 IU/ml of IFN-γ did not change their DNA histogram pattern. An immunoblotting with the antibodies to thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) in HCT-15 cells revealed that 0.1–10 IU/ml of IFN-γ enhanced their TS and DPD expressions. Results of the immunoblotting gave some explanation to attenuation in the sensitivity of HCT-15 cells to 5-FU.
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