Home > Publications Database > NF-κB in the Radiation Response of A549 Non-Small Cell Lung Cancer Cells to X-rays and Carbon Ions under Hypoxia. > print

001     269344
005     20240809090115.0
024 7 _ |a 10.3390/ijms25084495
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024 7 _ |a 1422-0067
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024 7 _ |a 1661-6596
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037 _ _ |a DZNE-2024-00513
041 _ _ |a English
082 _ _ |a 540
100 1 _ |a Nisar, Hasan
|0 0000-0001-5252-2212
|b 0
245 _ _ |a NF-κB in the Radiation Response of A549 Non-Small Cell Lung Cancer Cells to X-rays and Carbon Ions under Hypoxia.
260 _ _ |a Basel
|c 2024
|b Molecular Diversity Preservation International
336 7 _ |a article
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336 7 _ |a ARTICLE
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520 _ _ |a 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.
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650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a NF-kappa B: metabolism
|2 MeSH
650 _ 2 |a A549 Cells
|2 MeSH
650 _ 2 |a Carcinoma, Non-Small-Cell Lung: metabolism
|2 MeSH
650 _ 2 |a Carcinoma, Non-Small-Cell Lung: radiotherapy
|2 MeSH
650 _ 2 |a Carcinoma, Non-Small-Cell Lung: pathology
|2 MeSH
650 _ 2 |a Carcinoma, Non-Small-Cell Lung: genetics
|2 MeSH
650 _ 2 |a Lung Neoplasms: metabolism
|2 MeSH
650 _ 2 |a Lung Neoplasms: radiotherapy
|2 MeSH
650 _ 2 |a Lung Neoplasms: pathology
|2 MeSH
650 _ 2 |a Lung Neoplasms: genetics
|2 MeSH
650 _ 2 |a X-Rays
|2 MeSH
650 _ 2 |a Gene Expression Regulation, Neoplastic: radiation effects
|2 MeSH
650 _ 2 |a Linear Energy Transfer
|2 MeSH
650 _ 2 |a Cell Hypoxia: radiation effects
|2 MeSH
650 _ 2 |a Carbon
|2 MeSH
650 _ 2 |a Cell Survival: radiation effects
|2 MeSH
650 _ 2 |a Radiation Tolerance
|2 MeSH
650 _ 2 |a Interleukin-8: metabolism
|2 MeSH
650 _ 2 |a Interleukin-8: genetics
|2 MeSH
650 _ 7 |a NF-κB
|2 Other
650 _ 7 |a 12C ions
|2 Other
650 _ 7 |a A549
|2 Other
650 _ 7 |a IL-6/IL-8 secretion
|2 Other
650 _ 7 |a NF-κB
|2 Other
650 _ 7 |a high-LET radiation
|2 Other
650 _ 7 |a hypoxia-induced radioresistance
|2 Other
650 _ 7 |a p65 (RelA) nuclear localization
|2 Other
650 _ 7 |a tumor hypoxia
|2 Other
650 _ 7 |a NF-kappa B
|2 NLM Chemicals
650 _ 7 |a Carbon
|0 7440-44-0
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650 _ 7 |a Interleukin-8
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700 1 _ |a Sanchidrián González, Paulina Mercedes
|0 0009-0004-1596-9911
|b 1
700 1 _ |a Labonté, Frederik M
|b 2
700 1 _ |a Schmitz, Claudia
|b 3
700 1 _ |a Roggan, Marie Denise
|0 P:(DE-2719)9002551
|b 4
700 1 _ |a Kronenberg, Jessica
|b 5
700 1 _ |a Konda, Bikash
|b 6
700 1 _ |a Chevalier, François
|0 0000-0002-8488-2324
|b 7
700 1 _ |a Hellweg, Christine E
|0 0000-0002-2223-3580
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773 _ _ |a 10.3390/ijms25084495
|g Vol. 25, no. 8, p. 4495 -
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|t International journal of molecular sciences
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