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Is the resistance of gemcitabine for pancreatic cancer settled only by overexpression of deoxycytidine kinase?

  • Naotake Funamizu
  • , Aikou Okamoto
  • , Yuko Kamata
  • , Takeyuki Misawa
  • , Tadashi Uwagawa
  • , Takeshi Gocho
  • , Katsuhiko Yanaga
  • , Yoshinobu Manome
  • The Jikei University School of Medicine

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

The prognosis of pancreatic cancer remains poor, and the standard first-line chemotherapy with gemcitabine (GEM) has a response rate of less than 20%. Since expression of deoxycytidine kinase (dCK) seems important for improvement of GEM sensitivity, overexpression of dCK was investigated using pancreatic cancer cell lines (Panc-1, MIAPaCa-2 and BxPC-3). dCK gene was introduced into the cell lines by retrovirus and changes in IC50 were examined. Sensitivity of two pancreatic cancer cell lines to GEM elevated dramatically in comparison with control cells, but change of sensitivity remained at 1.8 times in BxPC-3. Since addition of tetrahydro uridine (THU), an inhibitor of deoxycytidine deaminase (CDA), increased the sensitivity 54-fold, overexpression of CDA seems to be the mechanism for improvement of the sensitivity. In conclusion, dCK is a key enzyme of GEM, but resistance of GEM is not improved in all pancreatic cancer cells by overexpression of dCK. Combination treatment based on expression of GEM metabolism-related gene may become an effective therapy in the future.

Original languageEnglish
Pages (from-to)471-475
Number of pages5
JournalOncology Reports
Volume23
Issue number2
DOIs
StatePublished - Feb 2010
Externally publishedYes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

Keywords

  • Deoxycytidine deaminase
  • Deoxycytidine kinase
  • Gemcitabine
  • Pancreatic cancer
  • Tetra-hydro uridine

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