In vitro enhancement of fluoropyrimidine-induced cytotoxicity by leucovorin in colorectal and gastric carcinoma cell lines but not in non-small-cell lung carcinoma cell lines

Yoshikazu Sugimoto, Yuichiro Ohe, Kazuto Nishio, Tohru Ohmori, Yasuhiro Fujiwara, Nagahiro SAijo

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Leucovorin (LV) increases the cytotoxic effect of fluorouracil (FUra) and 5-fluoro-2′-deoxyuridine (FdUrd) by enhancing the formation of the fluorodeoxyuridine monophosphate (FdUMP) thymidylate synthase (TS) 5,10-methylenetetrahydrofolate (mTHF) ternary complex. To study the difference in the efficacy of this combination against different tumors, we compared the effect of LV (20 μm) on the cytotoxicity of FUra, FdUrd, and 5-fluorouridine (FUrd) in vitro against cell lines of five colorectal carcinomas (CC), five gastric carcinomas (GC), and four non-small-cell lung carcinomas (NSCLC) using the colony-forming assay. At the concentration used in the experiments, LV alone failed to inhibit colony formation in any of the cell lines tested. The NSCLC cell lines were more resistant to FdUrd than were the CC and GC lines. LV modulated the cytotoxicity of FdUrd in all five CC lines and in three of the five GC lines but failed to do so in any of the NSCLC lines. In addition, following 20 h treatment with 1 μm [3H]-FdUrd, formation of the FdUMP/TS/mTHF ternary complex was enhanced by LV in the LV-sensitized CC and GC cell lines but not in the LV-refractory NSCLC lines. These in vitro data corresponded well to the results of clinical trials. Therefore, the colony-forming assay may be useful for the identification of the sensitivity of tumors according to phenotype.

Original languageEnglish
Pages (from-to)417-422
Number of pages6
JournalCancer Chemotherapy and Pharmacology
Volume30
Issue number6
DOIs
Publication statusPublished - 1992 Nov
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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