Biochemical modulation of 5-fluorouracil with murine interferon-α/β against murine renal cell carcinoma

Ken Marumo, Mototsugu Oya, Masaru Murai

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Abstract

Background: Conventional therapy for renal cell carcinoma using interferon (IFN) has shown limited antitumor action. The purpose of our study was to investigate synergistic antitumor effects of IFN and 5-fluorouracil (5-FU), and to elucidate the mechanisms of interaction between the 2 agents in mice. Methods: Antitumor effects and biochemical modulation of murine IFN-α/β and 5-FU were determined against the murine renal cell carcinoma cell line, Renca, in vivo. The activity of thymidylate synthetase and thymidine kinase was measured using cytosolic extract of the tumors. Results: Combination treatment with IFN-α/β and 5-FU produced a significant enhancement of growth inhibition against Renca tumor. Treatment with 5-FU resulted in a 2.7-fold increase in the total amount of thymidylate synthetase and an 11.6-fold increase in the thymidylate synthetase inhibition rate, while the administration of IFN-α/β did not significantly reduce the 5-FU-induced increase in thymidylate synthetase. The administration of IFN-α/β decreased thymidine kinase activity to 65.5% maximally, compared with that in the control mice or the mice treated with 5-FU. Conclusions: The reduction of thymidine kinase caused by treating the mice with IFN-α/β changes the utilization of exogenous thymidine for DNA synthesis, and may represent the mechanism of the additive antitumor effect of the 2 agents, through the suppression of the salvage pathway for deoxythymidine monophosphate induction.

Original languageEnglish
Pages (from-to)163-168
Number of pages6
JournalInternational Journal of Urology
Volume4
Issue number2
DOIs
Publication statusPublished - 1997 Jan 1

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Keywords

  • 5-fluorouracil
  • Biochemical modulation
  • Interferon
  • Mouse
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Urology

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