Browse by author
Lookup NU author(s): Dr Michael Tilby
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
BACKGROUND: Hypoxia is as an indicator of poor treatment outcome. Consistently, hypoxic HCT116 colorectal cancer cells are resistant to oxaliplatin, although the mechanistic basis is unclear. This study sought to investigate the relative contribution of HIF-1 (hypoxia-inducible factor-1)-mediated gene expression and drug penetrance to oxaliplatin resistance using three-dimensional spheroids. METHODS: Hypoxia-inducible factor-1 alpha function was suppressed by the stable expression of a dominant-negative form in HCT116 cells (DN). Cells were drug exposed as monolayer or multicellular spheroid cultures. Cells residing at differing oxygenation status were isolated from Hoechst 33342-treated spheroids using flow cytometry. Sub-populations were subjected to clonogenic survival assays and to Inductively-Coupled Plasma Mass Spectroscopy to determine oxaliplatin uptake. RESULTS: In spheroids, a sensitivity gradient (hypoxic
Author(s): Roberts DL, Williams KJ, Cowen RL, Barathova M, Eustace AJ, Brittain-Dissont S, Tilby MJ, Pearson DG, Ottley CJ, Stratford IJ, Dive C
Publication type: Article
Publication status: Published
Journal: British Journal of Cancer
Year: 2009
Volume: 101
Issue: 8
Pages: 1290-1297
ISSN (print): 0007-0920
ISSN (electronic): 1532-1827
Publisher: Nature Publishing Group
URL: http://dx.doi.org/10.1038/sj.bjc.6605311
DOI: 10.1038/sj.bjc.6605311
Altmetrics provided by Altmetric