Dual Modulation by l-Leucovorin and Recombinant Human Interferon α2a of 5-Fluorouracil Antitumor Activity Against the Human Colon Carcinoma Xenograft Co-4

Suguru Kase, Tetsuro Kubota, Masahiko Watanabe, Toshiharu Furukawa, Hirokazu Tanino, Tsong Hong Kuo, Yoshiro Saikawa, Tatsuo Teramoto, Masaki Kitajima

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We investigated the dual modulation by l-leucovorin (LV) and recombinant human interferon-α2a (IFN-α2a) 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-α2a 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-α2a 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
Issue number12
Publication statusPublished - 1995 Dec


ASJC Scopus subject areas

  • Immunology
  • Cell Biology
  • Virology

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