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000269344 1001_ $$00000-0001-5252-2212$$aNisar, Hasan$$b0
000269344 245__ $$aNF-κB in the Radiation Response of A549 Non-Small Cell Lung Cancer Cells to X-rays and Carbon Ions under Hypoxia.
000269344 260__ $$aBasel$$bMolecular Diversity Preservation International$$c2024
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000269344 520__ $$aCellular 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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000269344 650_2 $$2MeSH$$aHumans
000269344 650_2 $$2MeSH$$aNF-kappa B: metabolism
000269344 650_2 $$2MeSH$$aA549 Cells
000269344 650_2 $$2MeSH$$aCarcinoma, Non-Small-Cell Lung: metabolism
000269344 650_2 $$2MeSH$$aCarcinoma, Non-Small-Cell Lung: radiotherapy
000269344 650_2 $$2MeSH$$aCarcinoma, Non-Small-Cell Lung: pathology
000269344 650_2 $$2MeSH$$aCarcinoma, Non-Small-Cell Lung: genetics
000269344 650_2 $$2MeSH$$aLung Neoplasms: metabolism
000269344 650_2 $$2MeSH$$aLung Neoplasms: radiotherapy
000269344 650_2 $$2MeSH$$aLung Neoplasms: pathology
000269344 650_2 $$2MeSH$$aLung Neoplasms: genetics
000269344 650_2 $$2MeSH$$aX-Rays
000269344 650_2 $$2MeSH$$aGene Expression Regulation, Neoplastic: radiation effects
000269344 650_2 $$2MeSH$$aLinear Energy Transfer
000269344 650_2 $$2MeSH$$aCell Hypoxia: radiation effects
000269344 650_2 $$2MeSH$$aCarbon
000269344 650_2 $$2MeSH$$aCell Survival: radiation effects
000269344 650_2 $$2MeSH$$aRadiation Tolerance
000269344 650_2 $$2MeSH$$aInterleukin-8: metabolism
000269344 650_2 $$2MeSH$$aInterleukin-8: genetics
000269344 650_7 $$2Other$$aNF-κB
000269344 650_7 $$2Other$$a12C ions
000269344 650_7 $$2Other$$aA549
000269344 650_7 $$2Other$$aIL-6/IL-8 secretion
000269344 650_7 $$2Other$$aNF-κB
000269344 650_7 $$2Other$$ahigh-LET radiation
000269344 650_7 $$2Other$$ahypoxia-induced radioresistance
000269344 650_7 $$2Other$$ap65 (RelA) nuclear localization
000269344 650_7 $$2Other$$atumor hypoxia
000269344 650_7 $$2NLM Chemicals$$aNF-kappa B
000269344 650_7 $$07440-44-0$$2NLM Chemicals$$aCarbon
000269344 650_7 $$2NLM Chemicals$$aInterleukin-8
000269344 7001_ $$00009-0004-1596-9911$$aSanchidrián González, Paulina Mercedes$$b1
000269344 7001_ $$aLabonté, Frederik M$$b2
000269344 7001_ $$aSchmitz, Claudia$$b3
000269344 7001_ $$0P:(DE-2719)9002551$$aRoggan, Marie Denise$$b4
000269344 7001_ $$aKronenberg, Jessica$$b5
000269344 7001_ $$aKonda, Bikash$$b6
000269344 7001_ $$00000-0002-8488-2324$$aChevalier, François$$b7
000269344 7001_ $$00000-0002-2223-3580$$aHellweg, Christine E$$b8
000269344 773__ $$0PERI:(DE-600)2019364-6$$a10.3390/ijms25084495$$gVol. 25, no. 8, p. 4495 -$$n8$$p4495$$tInternational journal of molecular sciences$$v25$$x1422-0067$$y2024
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