NF-κB in the Radiation Response of A549 Non-Small Cell Lung Cancer Cells to X-rays and Carbon Ions under Hypoxia
Abstract
:1. Introduction
2. Results
2.1. Expression of NF-κB Target Genes in A549 Cells after Exposure to X-rays or Carbon Ions under Normoxia and Hypoxia
2.2. Secretion of the Cytokines IL-6 and IL-8 by A549 Cells after Exposure to X-rays or Carbon Ions under Normoxia and Hypoxia
3. Discussion
3.1. Irradiation Upregulates NF-κB Target Genes Influencing Apoptosis, Cell Cycle, and Cell Migration in A549 Cells
3.2. High-LET Radiation Enhances NF-κB Target Genes Expression in A549 Cells Compared to Low-LET Radiation
3.3. Chronic Hypoxia Upregulates NF-κB Target Genes Influencing Cell Survival and Cell Migration in A549 Cells
3.4. NF-κB Target Genes’ Activation Signature Following Irradiation May Promote Cancer Progression under Hypoxia, Especially after X-ray Exposure
3.5. Chronic Hypoxia Results in an Inflammatory Response in A549 Cells Distinct from Normoxia, Irrespective of Irradiation Status
4. Materials and Methods
4.1. Cell Line and Cultivation
4.2. Irradiation
4.3. Gene Expression Analysis
4.4. Quantification of Cytokines
4.5. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Regulated DEGs (Gene Name Abbreviation) | Gene Expression Based on p-Adjusted log2 Fold Changes | ||||||
---|---|---|---|---|---|---|---|
Irradiated vs. Unirradiated | Hypoxic vs. Normoxic | ||||||
X-rays | 12C Ions | Controls (H0 vs. N0) | X-rays (H8 vs. N8) | 12C Ions (H8 vs. N8) | |||
Normoxia (N8 a vs. N0) | Hypoxia (H8 vs. H0) | Normoxia (N8 vs. N0) | Hypoxia (H8 vs. H0) | ||||
FAS | 2.06 | 2.75 | 2.31 | 2.85 | −0.71 | −0.02 | −0.17 |
NTN1 | 1.36 | 1.93 | 2.19 | 2.29 | −0.03 | 0.54 | 0.07 |
CDKN1A | 2.63 | 2.62 | 2.61 | 2.38 | −0.19 | −0.21 | −0.42 |
KITLG | 1.01 | 1.38 | 1.36 | 1.46 | −1.10 | −0.73 | −1.00 |
PLK3 | 1.28 | 1.14 | 1.13 | 1.16 | −0.26 | −0.40 | −0.23 |
IL1A | 1.37 | 1.54 | 0.43 | 1.26 | 2.63 | 2.81 | 3.46 |
EBI3 | 0.60 | 0.81 | 1.04 | 1.45 | −0.29 | −0.08 | 0.12 |
TFEC | 2.49 | N/A b | 2.95 | 2.87 | N/A | N/A | N/A |
REV3L | 0.78 | 1.08 | 0.79 | 0.89 | −0.43 | −0.13 | −0.33 |
PTAFR | 0.83 | 1.15 | 0.72 | 0.97 | −0.55 | −0.23 | −0.29 |
GAD1 | 0.70 | 0.76 | 0.69 | 1.32 | −0.63 | −0.57 | 0.00 |
BAX | 0.58 | 0.83 | 0.74 | 1.01 | −0.27 | −0.03 | 0.00 |
MX1 | 0.22 | 0.18 | 0.12 | 1.16 | −0.31 | −0.35 | 0.73 |
ALOX5 | 1.16 | 1.35 | 1.43 | 2.49 | 0.48 | 0.68 | 1.54 |
GADD45A | 1.11 | 0.95 | 0.77 | 0.55 | 0.18 | 0.02 | −0.04 |
CCR7 | 0.76 | 0.49 | 1.02 | 0.62 | 0.00 | −0.27 | −0.40 |
EMX1 | 1.33 | 0.48 | 3.10 | 2.55 | −0.71 | −1.56 | N/A |
KCTD11 | 0.26 | −0.02 | 0.16 | 0.34 | 1.96 | 1.67 | 2.14 |
ADAM19 | −0.19 | −0.04 | −0.15 | −0.02 | 1.46 | 1.60 | 1.58 |
INHBA | 0.15 | 0.28 | 0.05 | 0.19 | 1.41 | 1.55 | 1.55 |
MMP9 | 0.26 | 0.81 | −0.45 | −0.75 | 1.87 | 2.43 | 1.58 |
PDGFB | −0.17 | 0.15 | −0.21 | −0.08 | 1.63 | 1.95 | 1.75 |
F3 | −0.05 | −0.02 | −0.62 | 0.03 | 2.00 | 2.02 | 2.65 |
CXCL8 | −0.15 | 0.03 | 0.01 | 0.10 | 1.31 | 1.49 | 1.41 |
SERPINE1 | 0.37 | 0.57 | 0.09 | 0.36 | 1.64 | 1.84 | 1.91 |
IL6 | 0.37 | 0.32 | 0.65 | 0.70 | 1.23 | 1.18 | 1.28 |
CARD11 | 0.00 | 0.14 | −0.17 | 0.20 | 1.05 | 1.18 | 1.42 |
BCL2A1 | 0.54 | 0.58 | 0.19 | −0.17 | 1.54 | 1.59 | 1.18 |
JUNB | −0.18 | −0.03 | −0.10 | 0.09 | 1.21 | 1.36 | 1.40 |
EGOT | 0.73 | 1.03 | −1.68 | 0.65 | 1.94 | 2.24 | N/A |
IL1B | 0.56 | 1.33 | 1.94 | 0.19 | 1.80 | 2.58 | 0.05 |
SOX9 | −0.57 | −0.11 | 0.12 | −0.11 | 1.01 | 1.47 | 0.79 |
CCL28 | 0.83 | −0.19 | −0.34 | 0.26 | 1.49 | 0.47 | 2.09 |
CD274 | −0.26 | −0.06 | −0.26 | −0.11 | 0.91 | 1.11 | 1.05 |
TRAF1 | 0.16 | 0.51 | 0.19 | −0.21 | 0.98 | 1.32 | 0.58 |
SNAI1 | −0.68 | 0.25 | −0.52 | −0.21 | 0.32 | 1.24 | 0.63 |
CCL20 | −1.45 | −0.02 | 0.63 | −0.10 | 0.62 | 2.05 | −0.11 |
LIPG | −0.28 | 0.66 | −0.09 | 0.21 | 0.53 | 1.47 | 0.83 |
ENO2 | 0.06 | −0.20 | −0.29 | −0.02 | 0.82 | 0.56 | 1.08 |
CCL2 | 0.16 | 0.27 | −0.02 | 0.25 | 0.89 | 1.00 | 1.17 |
PGK1 | 0.24 | 0.03 | −0.49 | 0.08 | 0.92 | 0.70 | 1.49 |
AGT | 0.39 | −0.38 | −1.30 | 1.56 | 0.02 | −0.75 | 2.88 |
ICAM1 | 0.19 | 0.45 | −0.23 | 0.33 | 0.52 | 0.78 | 1.09 |
GADD45B | 0.07 | 0.01 | −0.03 | 0.16 | 0.99 | 0.93 | 1.19 |
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Nisar, H.; Sanchidrián González, P.M.; Labonté, F.M.; Schmitz, C.; Roggan, M.D.; Kronenberg, J.; Konda, B.; Chevalier, F.; Hellweg, C.E. NF-κB in the Radiation Response of A549 Non-Small Cell Lung Cancer Cells to X-rays and Carbon Ions under Hypoxia. Int. J. Mol. Sci. 2024, 25, 4495. https://doi.org/10.3390/ijms25084495
Nisar H, Sanchidrián González PM, Labonté FM, Schmitz C, Roggan MD, Kronenberg J, Konda B, Chevalier F, Hellweg CE. NF-κB in the Radiation Response of A549 Non-Small Cell Lung Cancer Cells to X-rays and Carbon Ions under Hypoxia. International Journal of Molecular Sciences. 2024; 25(8):4495. https://doi.org/10.3390/ijms25084495
Chicago/Turabian StyleNisar, Hasan, Paulina Mercedes Sanchidrián González, Frederik M. Labonté, Claudia Schmitz, Marie Denise Roggan, Jessica Kronenberg, Bikash Konda, François Chevalier, and Christine E. Hellweg. 2024. "NF-κB in the Radiation Response of A549 Non-Small Cell Lung Cancer Cells to X-rays and Carbon Ions under Hypoxia" International Journal of Molecular Sciences 25, no. 8: 4495. https://doi.org/10.3390/ijms25084495