Contribution of HIF-1 and drug penetrance to oxaliplatin resistance in hypoxic colorectal cancer cells.
Authors
Roberts, Darren LWilliams, Kaye J
Cowen, Rachel L
Barathova, M
Eustace, A J
Brittain-Dissont, S
Tilby, Michael J
Pearson, D Graham
Ottley, Christopher J
Stratford, Ian J
Dive, Caroline
Affiliation
Paterson Institute for Cancer Research, University of Manchester, Manchester, UK.Issue Date
2009-10-20
Metadata
Show full item recordAbstract
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-1alpha 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 (hypoxicCitation
Contribution of HIF-1 and drug penetrance to oxaliplatin resistance in hypoxic colorectal cancer cells. 2009, 101 (8):1290-7 Br. J. CancerJournal
British Journal of CancerDOI
10.1038/sj.bjc.6605311PubMed ID
19755992Type
ArticleLanguage
enISSN
1532-1827ae974a485f413a2113503eed53cd6c53
10.1038/sj.bjc.6605311