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Small interfering RNA targeting HIF-1α reduces hypoxia-dependent transcription and radiosensitizes hypoxic HT 1080 human fibrosarcoma cells in vitro = Hypoxia-inducible-Factor-1α-Small-Interfering-RNA inhibiert die hypoxische Akkumulation von HIF-1 α und erhöht die Strahlensensitivität von HT-1080-Fibrosarkomzellen in vitro

Staab, Adrian ; Fleischer, Markus ; Loeffler, Juergen ; Said, Harun ; Katzer, Astrid ; Plathow, Christian ; Einsele, Herrmann ; Flentje, Michael ; Vordermark, Dirk

In: Strahlentherapie und Onkologie, 2011, vol. 187, no. 4, p. 252-259

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    Titre
    • Small interfering RNA targeting HIF-1α reduces hypoxia-dependent transcription and radiosensitizes hypoxic HT 1080 human fibrosarcoma cells in vitro
    Titre traduit ()
    • Hypoxia-inducible-Factor-1α-Small-Interfering-RNA inhibiert die hypoxische Akkumulation von HIF-1 α und erhöht die Strahlensensitivität von HT-1080-Fibrosarkomzellen in vitro
    Auteur
    • Staab, Adrian. Department of Radiation Oncology, University of Würzburg, Würzburg, Germany
    • Fleischer, Markus. Department of Radiation Oncology, University of Würzburg, Würzburg, Germany
    • Loeffler, Juergen. Medical Clinic II, University of Würzburg, Würzburg, Germany
    • Said, Harun. Department of Radiation Oncology, University of Würzburg, Würzburg, Germany
    • Katzer, Astrid. Department of Radiation Oncology, University of Würzburg, Würzburg, Germany
    • Plathow, Christian. Department of Nuclear Medicine, University of Freiburg, Freiburg, Germany
    • Einsele, Herrmann. Medical Clinic II, University of Würzburg, Würzburg, Germany
    • Flentje, Michael. Department of Radiation Oncology, University of Würzburg, Würzburg, Germany
    • Vordermark, Dirk. Department of Radiation Oncology, University of Würzburg, Würzburg, Germany
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Strahlentherapie und Onkologie, 2011, vol. 187, no. 4, p. 252-259. Urban and Vogel
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:311317
    Summary
    Background: : Hypoxia inducible factor-1 has been identified as a potential target to overcome hypoxia-induced radioresistance The aim of the present study was to investigate whether selective HIF-1 inhibition via small interfering RNA (siRNA) targeting hypoxia-inducible factor 1α (HIF-1α) affects hypoxia-induced radioresistance in HT 1080 human fibrosarcoma cells. Material and Methods: : HIF-1α expression in HT 1080 human fibrosarcoma cells in vitro was silenced using HIF-1α siRNA sequence primers. Quantitative real-time polymerase chain reaction assay was performed to quantify the mRNA expression of HIF-1α. HIF-1α protein levels were studied by Western blotting at 20% (air) or after 12 hours at 0.1% O2 (hypoxia). Cells were assayed for clonogenic survival after irradiation with 2, 5, or 10 Gy, under normoxic or hypoxic conditions in the presence of HIF-1α-targeted or control siRNA sequences. A modified oxygen enhancement ratio (OER´) was calculated as the ratio of the doses to achieve the same survival at 0.1% O2 as at ambient oxygen tensions. OER´ was obtained at cell survival levels of 50%, 37%, and 10%. Results: : HIF-1α-targeted siRNA enhanced radiation treatment efficacy under severely hypoxic conditions compared to tumor cells treated with scrambled control siRNA. OER was reduced on all survival levels after treatment with HIF-1α-targeted siRNA, suggesting that inhibition of HIF-1 activation by using HIF-1α-targeted siRNA increases radiosensitivity of hypoxic tumor cells in vitro. Conclusion: : Inhibition of HIF-1 activation by using HIF-1α-targeted siRNA clearly acts synergistically with radiotherapy and increase radiosensitivity of hypoxic cells in vitro