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

研究成果: Article査読

7 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)417-422
ページ数6
ジャーナルCancer Chemotherapy and Pharmacology
30
6
DOI
出版ステータスPublished - 1992 11
外部発表はい

ASJC Scopus subject areas

  • 腫瘍学
  • 毒物学
  • 薬理学
  • 癌研究
  • 薬理学(医学)

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