Abstract
Reduced folates have been shown to increase the cytotoxicity of 5-fluorouracil (5-FU) by stabilizing the 5-fluoro-2′-deoxyuridine-5′-monophosphate-thymidylate synthase complex, thus increasing the block in the DNA synthetic pathway. Using an in vitro colorimetric [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] cytotoxicity assay, we tested the effects of 5-FU and 5-fluoro-2′-deoxyuridine (FdUrd) with and without leucovorin (LV) on a panel of 11 human colorectal carcinoma cell lines. The effect of LV on 5-FU and FdUrd was quantitatively similar. A clinically achievable level of LV (20 μM) increased the cytotoxicity in all three replicate experiments in 10 of the 11 cell lines (P < .05, binomial test). LV alone at a concentration of 20 μM had no effect on cell survival. In three cell lines, 50% inhibition of growth occurred at a clinically achievable area under the curve of 5-FU alone. With the addition of LV, one additional cell line showed 50% growth inhibition at a clinically achievable level of 5-EU. Hence large clinical trials may be necessary to detect a significant improvement in survival as a result of adding LV to the fluorinated pyrimidines. [J Nail Cancer Inst 188;80:1560-1564]
Original language | English (US) |
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Pages (from-to) | 1560-1564 |
Number of pages | 5 |
Journal | Journal of the National Cancer Institute |
Volume | 80 |
Issue number | 19 |
DOIs | |
State | Published - Jul 7 1988 |
ASJC Scopus subject areas
- Oncology
- Cancer Research