Cancer Chemotherapy and Pharmacology

, Volume 64, Issue 1, pp 183–188 | Cite as

MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents

  • Erica L. Woodahl
  • Matthew H. Crouthamel
  • Tot Bui
  • Danny D. Shen
  • Rodney J. Y. Ho
Short Communication



P-glycoprotein (P-gp), encoded by MDR1 (or ABCB1), is important in anticancer drug delivery and resistance. We evaluated alterations in P-gp-mediated transport of anticancer agents due to the MDR1 G1199A polymorphism.


Using stable recombinant epithelial cells expressing wild-type (MDR1 wt ) or G1199A (MDR1 1199A ), anticancer drug sensitivity and transepithelial permeability were evaluated.


The recombinant cells MDR1 wt and MDR1 1199A displayed comparable doxorubicin resistance. However, MDR1 1199A cells displayed greater resistance to vinblastine, vincristine, paclitaxel, and VP-16 (11-, 2.9-, 1.9-, and 2.9-fold, respectively). Alterations in transepithelial permeability paralleled these changes. Efflux of doxorubicin was similar between MDR1 wt - and MDR1 1199A -expressing cells, while P-gp-mediated transport was greater for vinblastine and vincristine in MDR1 1199A cells (2.9- and 2.0-fold, respectively).


The occurrence and magnitude of the MDR1 G1199A effect is drug specific. Overall, the MDR1 G1199A polymorphism may impact anticancer efficacy through modulation of drug distribution and delivery to target tumor cells.


MDR1 ABCB1 P-Glycoprotein Pharmacogenomics Cancer chemotherapy Transepithelial permeability 



Multidrug resistance gene




ATP-binding cassette




Single nucleotide polymorphism


Wild-type MDR1


MDR1 G1199A polymorphism


Effective drug concentration necessary for 50% cell death


Transepithelial electrical resistance values


Apparent permeability


Apical-to-basolateral apparent permeability


Basolateral-to-apical apparent permeability



Supported in part by NIH grants GM62883, AI52663, NS39178, ES07033, and HL56548. ELW is a recipient of the NIH Pharmaceutical Sciences Training Grant (GM07750), and the William E. Bradley Fellowship in Pharmaceutics. Sequencing work was supported by the University School of Pharmacy DNA Sequencing and Gene Analysis Center. RJYH is also supported by the Milo Gibaldi Endowment.


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Erica L. Woodahl
    • 1
    • 2
  • Matthew H. Crouthamel
    • 1
  • Tot Bui
    • 1
  • Danny D. Shen
    • 1
  • Rodney J. Y. Ho
    • 1
  1. 1.Department of PharmaceuticsUniversity of WashingtonSeattleUSA
  2. 2.Department of Biomedical and Pharmaceutical SciencesUniversity of MontanaMissoulaUSA

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