HIF-1alpha role in oxygen-dependent radio- and chemosensitivity

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dc.contributor.advisor Allshire, Ashley en
dc.contributor.author Gebolys, Kinga
dc.date.accessioned 2015-08-13T14:07:03Z
dc.date.issued 2014
dc.date.submitted 2014
dc.identifier.citation Gebolys, K. 2014. HIF-1alpha role in oxygen-dependent radio- and chemosensitivity. PhD Thesis, University College Cork. en
dc.identifier.endpage 234
dc.identifier.uri http://hdl.handle.net/10468/1905
dc.description.abstract Poor oxygenation (hypoxia) is a common characteristic of human solid tumours, and is associated with cell survival, metastasis and resistance to radio- and chemotherapies. Hypoxia-induced stabilisation of hypoxia-inducible factor-1α (HIF-1α) leads to changes in expression of various genes associated with growth, vascularisation and metabolism. However whether HIF-1α plays a causal role in promoting hypoxic resistance to antitumour therapies remains unclear. In this study we used pharmacological and genetic methods to investigate the HIF-1α contribution to radio- and chemoresistance in four cancer cell lines derived from cervical, breast, prostate and melanoma human tumours. Under normoxia or hypoxia (<0.2% or 0.5% oxygen) the cells were exposed to either a standard irradiation dose (6.2 Gy) or chemotherapeutic drug (cisplatin), and subsequent cell proliferation (after 7 days) was measured in terms of resazurin reduction. Oxygen-dependent radio- and chemosensitivity was evident in all wild type whereas it was reduced or abolished in HIF-1α (siRNA) knockdown cells. The effects of HIF-1α-modulating drugs (EDHB, CoCl2, deferoxamine to stabilise and R59949 to destabilise it) reflected both HIF-1α-dependent and independent mechanisms. Collectively the data show that HIF-1α played a causal role in our in vitro model of hypoxia-induced radioresistance whereas its contribution to oxygendependent sensitivity to cisplatin was less clear-cut. Although this behavior is likely to be conditioned by further biological and physical factors operating in vivo, it is consistent with the hypothesis that interventions directed at HIF-1α may improve the clinical effectiveness of tumour treatments. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2014, Kinga Gebolys. en
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/ en
dc.subject HIF-1alpha en
dc.subject Cancer en
dc.subject Hypoxia en
dc.subject Oxygen-dependent radioresistance en
dc.subject Oxygen-dependent chemoresistance en
dc.title HIF-1alpha role in oxygen-dependent radio- and chemosensitivity en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PhD (Medicine and Health) en
dc.internal.availability Full text available en
dc.description.version Accepted Version
dc.contributor.funder Aid Cancer Treatment, Cork en
dc.description.status Not peer reviewed en
dc.internal.school Pharmacology and Therapeutics en
dc.check.reason This thesis is due for publication or the author is actively seeking to publish this material en
dc.check.opt-out Not applicable en
dc.thesis.opt-out false
dc.check.chapterOfThesis 3,4
dc.check.embargoformat E-thesis on CORA only en
ucc.workflow.supervisor a.allshire@ucc.ie
dc.internal.conferring Autumn Conferring 2014

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© 2014, Kinga Gebolys. Except where otherwise noted, this item's license is described as © 2014, Kinga Gebolys.
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