Increased sensitivity to gemcitabine of P-glycoprotein and multidrug resistance-associated protein-overexpressing human cancer cell lines

A. M. Bergman, H. M. Pinedo, I. Talianidis, G. Veerman, W. J P Loves, C. L. Van Der Wilt, G. J. Peters

Research output: Contribution to journalArticlepeer-review

Abstract

Gemcitabine (2′,2′-difluorodeoxycytidine) is a deoxycytidine analogue that is activated by deoxycytidine kinase (dCK) to its monophosphate and subsequently to its triphosphate dFdCTP, which is incorporated into both RNA and DNA, leading to DNA damage. Multidrug resistance (MDR) is characterised by an overexpression of the membrane efflux pumps P-glycoprotein (P-gP) or multidrug resistance-associated protein (MRP). Gemcitabine was tested against human melanoma, non-small-cell lung cancer, small-cell lung cancer, epidermoid carcinoma and ovarian cancer cells with an MDR phenotype as a result of selection by drug exposure or by transfection with the mdr1 gene. These cell lines were nine- to 72-fold more sensitive to gemcitabine than their parental cell lines. The doxorubicin-resistant cells 2R120 (MRP1) and 2R160 (P-gP) were nine- and 28-fold more sensitive to gemcitabine than their parental SW1573 cells, respectively (P3H]gemcitabine into DNA (P

Original languageEnglish (US)
Pages (from-to)1963-1970
Number of pages8
JournalBritish Journal of Cancer
Volume88
Issue number12
DOIs
StatePublished - Jun 16 2003
Externally publishedYes

Keywords

  • Collateral sensitivity
  • Deoxycytidine kinase
  • Gemcitabine
  • Multidrug resistance
  • Thymidine kinase

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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