Consensus interferon enhances the anti-proliferative effect of 5-fluorouracil on human hepatoma cells via downregulation of dihydropyrimidine dehydrogenase expression
Article first published online: 7 FEB 2005
Volume 25, Issue 1, pages 148–152, February 2005
How to Cite
Dou, J., Iwashita, Y., Sasaki, A., Kai, S., Hirano, S., Ohta, M. and Kitano, S. (2005), Consensus interferon enhances the anti-proliferative effect of 5-fluorouracil on human hepatoma cells via downregulation of dihydropyrimidine dehydrogenase expression. Liver International, 25: 148–152. doi: 10.1111/j.1478-3231.2005.01030.x
- Issue published online: 7 FEB 2005
- Article first published online: 7 FEB 2005
- Received 9 November 2003, accepted 15 September 2004
- consensus interferon;
- dihydropyrimidine dehydrogenase;
- reverse transcription-polymerase chain reaction;
Abstract: Background/Aims: The effectiveness of 5-fluorouracil (5-FU) treatment is influenced by the activities of pyrimidine catabolic enzymes. The aim of this study was to investigate whether interferon (IFN)-α influences expression of 5-FU catabolic or target-related enzymes in human hepatoma cells.
Methods: HepG2 cells were treated with 0, 0.15, 1.5, 15, and 150 ng/ml of consensus interferon (C-IFN). Expression of mRNAs encoding dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase, and thymidylate synthase was examined by reverse transcription-polymerase chain reaction before and after C-IFN treatment. To determine the effect of pretreatment with C-IFN on 5-FU+C-IFN combination therapy, we performed WST-1 cell proliferation assays.
Results: A significant reduction in the level of DPD mRNA was observed when HepG2 cells were pretreated with C-IFN (P<0.05). This reduction occurred in a time-dependent manner. Cell proliferation was reduced most significantly when HepG2 cells were treated with 5-FU and C-IFN. Furthermore, when cells were pretreated with C-IFN for 3 days, the anti-proliferative effect of 5-FU+C-IFN combination therapy was augmented significantly (P<0.05).
Conclusions: C-IFN likely improves the anti-tumor effect of 5-FU via downregulation of DPD enzyme in hepatoma cells. Pretreatment with C-IFN may increase the anti-cancer effect of 5-FU+C-IFN combination therapy.