Dihydropyrimidine dehydrogenase, multidrug resistance-associated protein, and thymidylate synthase gene expression levels can predict 5-fluorouracil resistance in human gastrointestinal cancer cells

Int J Oncol. 1999 Mar;14(3):551-6. doi: 10.3892/ijo.14.3.551.


Gene expression of dihydropyrimidine dehydrogenase (DPD) and newly multidrug resistance-associated protein (MRP) was found to correlate well with primary 5-FU resistance in 7 human gastrointestinal cancer cell lines. Although mRNA and protein levels of thymidylate synthase (TS) did not relate to the resistance, 5-FU treatment revealed a remarkable increase of TS expression. Such enhanced TS expression was more significant than DPD and MRP, and observed less in 5-FU sensitive cells. DPD and MRP expression levels can predict primary 5-FU resistance, and TS may be a potent predictor of cellular 5-FU resistance after 5-FU treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism*
  • Antimetabolites, Antineoplastic / pharmacology*
  • Biomarkers
  • Dihydrouracil Dehydrogenase (NADP)
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Drug Screening Assays, Antitumor
  • Fluorouracil / pharmacology*
  • Gastrointestinal Neoplasms / drug therapy
  • Gastrointestinal Neoplasms / enzymology*
  • Gastrointestinal Neoplasms / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Multidrug Resistance-Associated Proteins
  • Oxidoreductases / metabolism*
  • RNA, Messenger / metabolism
  • Thymidylate Synthase / metabolism*
  • Tumor Cells, Cultured


  • ATP-Binding Cassette Transporters
  • Antimetabolites, Antineoplastic
  • Biomarkers
  • Multidrug Resistance-Associated Proteins
  • RNA, Messenger
  • Oxidoreductases
  • Dihydrouracil Dehydrogenase (NADP)
  • Thymidylate Synthase
  • Fluorouracil