The modulation by L-leucovorin of 5-fluorouracil antitumor activity on human colon carcinoma cells in vitro and in vivo

Suguru Kase, Tetsuro Kubota, Masahiko Watanabe, Tetsuya Takahara, Tooru Takeuchi, Hiroshi Yamaguchi, Toshiharu Furukawa, Tatsuo Teramoto, Susumu Kodaira, Kyuya Ishibiki, Masaki Kitajima

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Abstract

We investigated the modulating effect of L-leucovorin (LV) on the antitumor effect of 5-fluorouracil (5-FU) against human colon carcinoma cells (C-1) in vitro and human colon carcinoma xenografts (Co-4) in nude mice. The modulating effect of LV on 5-FU reached an optimal concentration of 40-80 μg/ml in vitro which was detected by a colorimetric MTT assay. An optimal dose of 200 mg/kg was also observed in the nude mouse system. The modulating effect of LV increased according to the increment of thymidylate synthetase inhibition in vivo. Since the pharmacokinetic pattern of LV in the nude mice administered LV at 200 mg/kg was similar to that in patients treated with LV at a dose of 100 mg/m2, this clinical method of administration was thought to be adequate for modulating the antitumor activity of 5-FU against clinical colon carcinomas.

Original languageEnglish
Pages (from-to)615-620
Number of pages6
JournalSurgery today
Volume23
Issue number7
DOIs
Publication statusPublished - 1993 Jul 1

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Keywords

  • 5-fluorouracil
  • L-leucovorin
  • human colon carcinoma

ASJC Scopus subject areas

  • Surgery

Cite this

Kase, S., Kubota, T., Watanabe, M., Takahara, T., Takeuchi, T., Yamaguchi, H., Furukawa, T., Teramoto, T., Kodaira, S., Ishibiki, K., & Kitajima, M. (1993). The modulation by L-leucovorin of 5-fluorouracil antitumor activity on human colon carcinoma cells in vitro and in vivo. Surgery today, 23(7), 615-620. https://doi.org/10.1007/BF00311910