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 language | English (US) |
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Pages (from-to) | 37-46 |
Number of pages | 10 |
Journal | Cancer Letters |
Volume | 284 |
Issue number | 1 |
DOIs | |
State | Published - Oct 18 2009 |
Bibliographical note
Funding Information:These studies were supported, in part, by the Cancer and Leukemia Group B (CALGB) Foundation.
Keywords
- 4E-BP1
- Bioreactor
- Cap-dependent translation
- Gemcitabine
- Interaction