Contribution of HIF-1 and drug penetrance to oxaliplatin resistance in hypoxic colorectal cancer cells.
AuthorsRoberts, Darren L
Williams, Kaye J
Cowen, Rachel L
Eustace, A J
Tilby, Michael J
Pearson, D Graham
Ottley, Christopher J
Stratford, Ian J
AffiliationPaterson Institute for Cancer Research, University of Manchester, Manchester, UK.
MetadataShow full item record
AbstractBACKGROUND: 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 (hypoxic
CitationContribution of HIF-1 and drug penetrance to oxaliplatin resistance in hypoxic colorectal cancer cells. 2009, 101 (8):1290-7 Br. J. Cancer
JournalBritish Journal of Cancer
- Synergistic antitumor effects of endostar in combination with oxaliplatin via inhibition of HIF and CXCR4 in the colorectal cell line SW1116.
- Authors: Jin F, Ji H, Jia C, Brockmeier U, Hermann DM, Metzen E, Zhu Y, Chi B
- Issue date: 2012
- Metabolic targeting of HIF-1α potentiates the therapeutic efficacy of oxaliplatin in colorectal cancer.
- Authors: Wei TT, Lin YT, Tang SP, Luo CK, Tsai CT, Shun CT, Chen CC
- Issue date: 2020 Jan
- SN-38 overcomes chemoresistance of colorectal cancer cells induced by hypoxia, through HIF1alpha.
- Authors: Murono K, Tsuno NH, Kawai K, Sasaki K, Hongo K, Kaneko M, Hiyoshi M, Tada N, Nirei T, Sunami E, Takahashi K, Kitayama J
- Issue date: 2012 Mar
- Hypoxia Induces Drug Resistance in Colorectal Cancer through the HIF-1α/miR-338-5p/IL-6 Feedback Loop.
- Authors: Xu K, Zhan Y, Yuan Z, Qiu Y, Wang H, Fan G, Wang J, Li W, Cao Y, Shen X, Zhang J, Liang X, Yin P
- Issue date: 2019 Oct 2
- Luteolin sensitizes two oxaliplatin-resistant colorectal cancer cell lines to chemotherapeutic drugs via inhibition of the Nrf2 pathway.
- Authors: Chian S, Li YY, Wang XJ, Tang XW
- Issue date: 2014