Journal Article

DZNE-2025-01128

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Effect of Reoxygenation on Radioresistance of Chronically Hypoxic A549 Non-Small Cell Lung Cancer (NSCLC) Cells Following X-Ray and Carbon Ion Exposure.

Nisar, H. ; Konda, B. ; Roggan, M. D.DZNE* ; Labonté, F. M. ; Arif, M. ; Diegeler, S. ; Schmitz, C. ; Baumstark-Khan, C. ; Chevalier, F. ; Hellweg, C. E.

2025
Molecular Diversity Preservation International Basel

This record in other databases:    

Please use a persistent id in citations: doi:10.3390/ijms26189153

Abstract: 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.

Keyword(s): Humans (MeSH) ; Carcinoma, Non-Small-Cell Lung: metabolism (MeSH) ; Carcinoma, Non-Small-Cell Lung: radiotherapy (MeSH) ; Carcinoma, Non-Small-Cell Lung: pathology (MeSH) ; Carcinoma, Non-Small-Cell Lung: genetics (MeSH) ; Lung Neoplasms: metabolism (MeSH) ; Lung Neoplasms: radiotherapy (MeSH) ; Lung Neoplasms: pathology (MeSH) ; Lung Neoplasms: genetics (MeSH) ; Radiation Tolerance: drug effects (MeSH) ; X-Rays (MeSH) ; A549 Cells (MeSH) ; Oxygen: metabolism (MeSH) ; Oxygen: pharmacology (MeSH) ; Cell Survival: radiation effects (MeSH) ; Carbon (MeSH) ; Epithelial-Mesenchymal Transition: radiation effects (MeSH) ; Cell Hypoxia: radiation effects (MeSH) ; Interleukin-6: metabolism (MeSH) ; Gene Expression Regulation, Neoplastic: radiation effects (MeSH) ; Interleukin-8: metabolism (MeSH) ; DNA double-strand breaks ; DNA repair ; cell cycle ; epithelial–mesenchymal transition ; hypoxia ; interleukin expression ; ionizing radiation ; lung cancer ; non-small cell lung cancer cells ; radioresistance ; reoxygenation ; survival ; Oxygen ; Carbon ; Interleukin-6 ; Interleukin-8

---

Contributing Institute(s):

1. Neuroimmunology and Imaging (AG Fuhrmann)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2025

---

Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; Essential Science Indicators ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---