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@ARTICLE{Nisar:269344,
author = {Nisar, Hasan and Sanchidrián González, Paulina Mercedes
and Labonté, Frederik M and Schmitz, Claudia and Roggan,
Marie Denise and Kronenberg, Jessica and Konda, Bikash and
Chevalier, François and Hellweg, Christine E},
title = {{NF}-κ{B} in the {R}adiation {R}esponse of {A}549
{N}on-{S}mall {C}ell {L}ung {C}ancer {C}ells to {X}-rays and
{C}arbon {I}ons under {H}ypoxia.},
journal = {International journal of molecular sciences},
volume = {25},
number = {8},
issn = {1422-0067},
address = {Basel},
publisher = {Molecular Diversity Preservation International},
reportid = {DZNE-2024-00513},
pages = {4495},
year = {2024},
abstract = {Cellular hypoxia, detectable in up to $80\%$ of non-small
cell lung carcinoma (NSCLC) tumors, is a known cause of
radioresistance. High linear energy transfer (LET) particle
radiation might be effective in the treatment of hypoxic
solid tumors, including NSCLC. Cellular hypoxia can activate
nuclear factor κB (NF-κB), which can modulate
radioresistance by influencing cancer cell survival. The
effect of high-LET radiation on NF-κB activation in hypoxic
NSCLC cells is unclear. Therefore, we compared the effect of
low (X-rays)- and high (12C)-LET radiation on NF-κB
responsive genes' upregulation, as well as its target
cytokines' synthesis in normoxic and hypoxic A549 NSCLC
cells. The cells were incubated under normoxia $(20\%$ O2)
or hypoxia $(1\%$ O2) for 48 h, followed by irradiation with
8 Gy X-rays or 12C ions, maintaining the oxygen conditions
until fixation or lysis. Regulation of NF-κB responsive
genes was evaluated by mRNA sequencing. Secretion of NF-κB
target cytokines, IL-6 and IL-8, was quantified by ELISA. A
greater fold change increase in expression of NF-κB target
genes in A549 cells following exposure to 12C ions compared
to X-rays was observed, regardless of oxygenation status.
These genes regulate cell migration, cell cycle, and cell
survival. A greater number of NF-κB target genes was
activated under hypoxia, regardless of irradiation status.
These genes regulate cell migration, survival,
proliferation, and inflammation. X-ray exposure under
hypoxia additionally upregulated NF-κB target genes
modulating immunosurveillance and epithelial-mesenchymal
transition (EMT). Increased IL-6 and IL-8 secretion under
hypoxia confirmed NF-κB-mediated expression of
pro-inflammatory genes. Therefore, radiotherapy,
particularly with X-rays, may increase tumor invasiveness in
surviving hypoxic A549 cells.},
keywords = {Humans / NF-kappa B: metabolism / A549 Cells / Carcinoma,
Non-Small-Cell Lung: metabolism / Carcinoma, Non-Small-Cell
Lung: radiotherapy / Carcinoma, Non-Small-Cell Lung:
pathology / Carcinoma, Non-Small-Cell Lung: genetics / Lung
Neoplasms: metabolism / Lung Neoplasms: radiotherapy / Lung
Neoplasms: pathology / Lung Neoplasms: genetics / X-Rays /
Gene Expression Regulation, Neoplastic: radiation effects /
Linear Energy Transfer / Cell Hypoxia: radiation effects /
Carbon / Cell Survival: radiation effects / Radiation
Tolerance / Interleukin-8: metabolism / Interleukin-8:
genetics / NF-κB (Other) / 12C ions (Other) / A549 (Other)
/ IL-6/IL-8 secretion (Other) / NF-κB (Other) / high-LET
radiation (Other) / hypoxia-induced radioresistance (Other)
/ p65 (RelA) nuclear localization (Other) / tumor hypoxia
(Other) / NF-kappa B (NLM Chemicals) / Carbon (NLM
Chemicals) / Interleukin-8 (NLM Chemicals)},
cin = {AG Fuhrmann},
ddc = {540},
cid = {I:(DE-2719)1011004},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38674080},
pmc = {pmc:PMC11050661},
doi = {10.3390/ijms25084495},
url = {https://pub.dzne.de/record/269344},
}