Dual modulation by l-leucovorin and recombinant human interferon α(2a) of 5-fluorouracil antitumor activity against the human colon carcinoma xenograft Co-4

S. Kase, T. Kubota, M. Watanabe, Toshiharu Furukawa, H. Tanino, T. H. Kuo, Y. Saikawa, T. Teramoto, M. Kitajima

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Abstract

We investigated the dual modulation by l-leucovorin (LV) and recombinant human interferon-α(2a) (IFN-α(2a)) of 5-fluorouracil (5-FU) antitumor activity against human colon carcinoma cells (Co-4) using a nude mouse system. 5-FU was administered intraperitoneally (IP) at 10 or 90 mg/kg. 5-FU (10 mg/kg) was administered daily for 10 days, and 90 mg/kg was administered once. LV was administered IP 1 and 0 h before 5-FU treatment at 200 mg/kg. IFN-α(2a) was administered subcutaneously (SC) daily for 14 days at 60,000 IU/mouse. When 5-FU was administered at 10 or 90 mg/kg with these two modulators, the antitumor effect was increased significantly, with T/C ratios of 18.1 and 6.1, respectively. These modulatory effects were assessed as synergistic, without associated severe side effects or death during the experimental period. LV augmented the antitumor activity of 5-FU through increment of thymidylate synthetase (TS) inhibition, and IFN-α(2a) showed a modulatory effect in elevating the intratumoral concentration of fluorouridine without change in TS inhibition. These results suggest that 5- FU antitumor activity against human colon carcinoma could be significantly potentiated without severe side effects by these two modulators, which possess different modes of action.

Original languageEnglish
Pages (from-to)1089-1093
Number of pages5
JournalJournal of Interferon and Cytokine Research
Volume15
Issue number12
Publication statusPublished - 1995

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Leucovorin
Heterografts
Human Activities
Fluorouracil
Interferons
Colon
Carcinoma
Thymidylate Synthase
Nude Mice

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Cell Biology

Cite this

Dual modulation by l-leucovorin and recombinant human interferon α(2a) of 5-fluorouracil antitumor activity against the human colon carcinoma xenograft Co-4. / Kase, S.; Kubota, T.; Watanabe, M.; Furukawa, Toshiharu; Tanino, H.; Kuo, T. H.; Saikawa, Y.; Teramoto, T.; Kitajima, M.

In: Journal of Interferon and Cytokine Research, Vol. 15, No. 12, 1995, p. 1089-1093.

Research output: Contribution to journalArticle

Kase, S. ; Kubota, T. ; Watanabe, M. ; Furukawa, Toshiharu ; Tanino, H. ; Kuo, T. H. ; Saikawa, Y. ; Teramoto, T. ; Kitajima, M. / Dual modulation by l-leucovorin and recombinant human interferon α(2a) of 5-fluorouracil antitumor activity against the human colon carcinoma xenograft Co-4. In: Journal of Interferon and Cytokine Research. 1995 ; Vol. 15, No. 12. pp. 1089-1093.
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