Cap-dependent translation blockade and fixed dose-rate gemcitabine: Interaction in an in vitro bioreactor system

Brent W. Williams, Jessica J. Chang, Ruth M. Chi, Paul H. Marker, Chris D. Frethem, Chap T Le, Robert A Kratzke, Mark N Kirstein

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Translation initiation commences with the binding of eIF-4F to the mRNA 5′-end cap. eIF-4F binds the cap structure via its eIF-4E subunit, which is the rate-limiting step for the initiation of translation. This pathway can be inhibited by 4E-binding proteins (4E-BPs). The present study investigated prolonged gemcitabine infusion in combination with reduced eIF-4E function on NSCLC cell viability in an in vitro bioreactor system. To assess attachment to the hollow fibers, cells with dominant active 4E-BP1 were first analyzed by scanning electron microscopy. Cells were treated with 0.5- or 2.5 h (fixed dose rate) infusion (same total dose), simulating human plasma gemcitabine concentration-time profiles. An interaction was observed between fixed dose rate infusion gemcitabine and presence of dominant active 4E-BP1. We conclude that cap-dependent translation blockade and fixed dose rate infusion gemcitabine treatment results in a significant interaction affecting cell viability in vitro.

Original languageEnglish (US)
Pages (from-to)37-46
Number of pages10
JournalCancer Letters
Volume284
Issue number1
DOIs
StatePublished - Oct 18 2009

Keywords

  • 4E-BP1
  • Bioreactor
  • Cap-dependent translation
  • Gemcitabine
  • Interaction

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