Nisar, Hasan und Konda, Bikash und Hoffmann, Marie D. und Labonté, Frederik M. und Arif, Maryam und Diegeler, Sebastian und Schmitz, Claudia und Baumstark-Khan, Christa und Chevalier, François und Hellweg, Christine E. (2025) Effect of Reoxygenation on Radioresistance of Chronically Hypoxic A549 Non-Small Cell Lung Cancer (NSCLC) Cells Following X-Ray and Carbon Ion Exposure. International Journal of Molecular Sciences, 26 (18), Seite 9153. Multidisciplinary Digital Publishing Institute (MDPI). doi: 10.3390/ijms26189153. ISSN 1661-6596.
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Offizielle URL: https://dx.doi.org/10.3390/ijms26189153
Kurzfassung
Hypoxia-induced radioresistance in non-small cell lung cancer (NSCLC) hinders radiotherapy efficacy. Fractionated schedules exploit reoxygenation between fractions to reverse this resistance, but the effects of post-irradiation reoxygenation remain unclear and may depend on radiation quality. We investigated survival, cell cycle progression, cytokine secretion, and gene expression in hypoxic (1 % O₂) and reoxygenated A549 cells irradiated with X-rays or carbon ions. Colony-forming assays revealed an Oxygen Enhancement Ratio (OER) > 1 for both hypoxic and reoxygenated cells after X-rays, indicating persistent radioresistance; carbon ion OER ≈ 1 reflected oxygen-independent cytotoxicity. Hypoxia weakened radiation-induced G₂ arrest, and this was unaffected by reoxygenation. IL-6 secretion increased after X-rays and IL-8 after carbon ions exposure; both were enhanced under hypoxia and reoxygenation. RNA sequencing revealed that hypoxia induced a pro-survival, epithelial-to-mesenchymal transition (EMT)-promoting, and immune-evasive transcriptional program, which was largely reversed by reoxygenation but without increased clonogenic killing. These findings indicate that short-term reoxygenation after irradiation can normalize hypoxia-driven transcriptional changes yet does not restore radiosensitivity, supporting the advantage of high-linear energy transfer (LET) carbon ions for targeting resistant hypoxic NSCLC cells.
| elib-URL des Eintrags: | https://elib.dlr.de/216794/ | ||||||||||||||||||||||||||||||||||||||||||||
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| Dokumentart: | Zeitschriftenbeitrag | ||||||||||||||||||||||||||||||||||||||||||||
| Zusätzliche Informationen: | This article belongs to the Special Issue Molecular Perspectives in Lung Diseases: Pathogenesis, Diagnosis, and Treatment | ||||||||||||||||||||||||||||||||||||||||||||
| Titel: | Effect of Reoxygenation on Radioresistance of Chronically Hypoxic A549 Non-Small Cell Lung Cancer (NSCLC) Cells Following X-Ray and Carbon Ion Exposure | ||||||||||||||||||||||||||||||||||||||||||||
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| Datum: | 19 September 2025 | ||||||||||||||||||||||||||||||||||||||||||||
| Erschienen in: | International Journal of Molecular Sciences | ||||||||||||||||||||||||||||||||||||||||||||
| Referierte Publikation: | Ja | ||||||||||||||||||||||||||||||||||||||||||||
| Open Access: | Ja | ||||||||||||||||||||||||||||||||||||||||||||
| Gold Open Access: | Ja | ||||||||||||||||||||||||||||||||||||||||||||
| In SCOPUS: | Ja | ||||||||||||||||||||||||||||||||||||||||||||
| In ISI Web of Science: | Ja | ||||||||||||||||||||||||||||||||||||||||||||
| Band: | 26 | ||||||||||||||||||||||||||||||||||||||||||||
| DOI: | 10.3390/ijms26189153 | ||||||||||||||||||||||||||||||||||||||||||||
| Seitenbereich: | Seite 9153 | ||||||||||||||||||||||||||||||||||||||||||||
| Verlag: | Multidisciplinary Digital Publishing Institute (MDPI) | ||||||||||||||||||||||||||||||||||||||||||||
| ISSN: | 1661-6596 | ||||||||||||||||||||||||||||||||||||||||||||
| Status: | veröffentlicht | ||||||||||||||||||||||||||||||||||||||||||||
| Stichwörter: | ionizing radiation; hypoxia; reoxygenation; lung cancer; survival; cell cycle; DNA double-strand breaks; DNA repair; interleukin expression; non-small cell lung cancer cells; radioresistance; epithelial–mesenchymal transition | ||||||||||||||||||||||||||||||||||||||||||||
| HGF - Forschungsbereich: | Luftfahrt, Raumfahrt und Verkehr | ||||||||||||||||||||||||||||||||||||||||||||
| HGF - Programm: | Raumfahrt | ||||||||||||||||||||||||||||||||||||||||||||
| HGF - Programmthema: | Forschung unter Weltraumbedingungen | ||||||||||||||||||||||||||||||||||||||||||||
| DLR - Schwerpunkt: | Raumfahrt | ||||||||||||||||||||||||||||||||||||||||||||
| DLR - Forschungsgebiet: | R FR - Forschung unter Weltraumbedingungen | ||||||||||||||||||||||||||||||||||||||||||||
| DLR - Teilgebiet (Projekt, Vorhaben): | R - Strahlung & Hypoxie | ||||||||||||||||||||||||||||||||||||||||||||
| Standort: | Köln-Porz | ||||||||||||||||||||||||||||||||||||||||||||
| Institute & Einrichtungen: | Institut für Luft- und Raumfahrtmedizin > Strahlenbiologie Institut für Luft- und Raumfahrtmedizin > Leitungsbereich ME | ||||||||||||||||||||||||||||||||||||||||||||
| Hinterlegt von: | Kopp, Kerstin | ||||||||||||||||||||||||||||||||||||||||||||
| Hinterlegt am: | 24 Sep 2025 10:35 | ||||||||||||||||||||||||||||||||||||||||||||
| Letzte Änderung: | 24 Sep 2025 10:35 |
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