Positive interaction between 5-FU and FdUMP[10] in the inhibition of human colorectal tumor cell proliferation

Antisense Nucleic Acid Drug Dev. 1999 Oct;9(5):481-6. doi: 10.1089/oli.1.1999.9.481.


Interaction between 5-fluorouracil (5-FU) and FdUMP[10], a novel pro-drug formulation of the thymidylate synthase (TS) inhibitory nucleotide 5-fluoro-2'-deoxyuridine-5'-O-monophosphate (FdUMP), was investigated to evaluate the feasibility of using these two forms of fluorinated pyrimidine in combination chemotherapy regimens. 5-FU and FdUMP[10] are expected to differ in their relative intracellular distribution of active metabolites, and their combined administration may result in either a positive or a negative interactive effect. The dose-response behaviors of 5-FU and FdUMP[10] toward H630 and H630-10 (human colorectal tumor) cells were first investigated separately. Effects on cell viability were measured using an assay for 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), while cytotoxicity and apoptosis were investigated using clonogenic and TUNEL assays, respectively. Exposure of H630 cells to concentrations of FdUMP[10] insufficient to inhibit cell proliferation as a single agent markedly increased the cytotoxicity of 5-FU. The results indicate that 5-FU and FdUMP[10] interact in a positive manner, and that combining these two forms of fluorinated pyrimidine may be clinically beneficial.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology*
  • Cell Division / drug effects*
  • Colorectal Neoplasms / pathology*
  • Drug Synergism
  • Fluorodeoxyuridylate / pharmacology*
  • Fluorouracil / pharmacology*
  • Humans
  • Prodrugs / pharmacology
  • Tumor Cells, Cultured


  • Antimetabolites, Antineoplastic
  • Prodrugs
  • Fluorodeoxyuridylate
  • Fluorouracil