Effect of Carbon Ion Radiation Induces Bystander Effect on Metastasis of A549 Cells and Metabonomic Correlation Analysis

Abstract

ObjectiveTo analyze the effect of carbon ion (12C6+) radiation may induce bystander effect on A549 cell metastasis and metabonomics.MethodsA549 cell was irradiated with carbon ion to establish the clone survival model and the transwell matrix assay was applied to measure the effect of carbon ion on cell viability, migration, and invasion, respectively. Normal human embryonic lung fibroblasts (WI-38) were irradiated with carbon ions of 0 and 2 Gy and then transferred to A549 cell co-culture medium for 24 h. The migration and invasion of A549 cells were detected by the Transwell chamber. The analysis of metabonomic information in transfer medium by liquid phase mass spectrometry (LC-MS), The differential molecules were obtained by principal pomponent analysis (PCA) and the target proteins of significant differences (p = 1.7 × 10−3) obtained by combining with the STICH database. KEGG pathway was used to analyze the enrichment of the target protein pathway.ResultsCompared with 0 Gy, the colony formation, migration, and invasion of A549 cells were significantly inhibited by carbon ion 2 and 4 Gy irradiation, while the inhibitory effect was not significant after 1 Gy irradiation. Compared with 0 Gy, the culture medium 24 h after carbon ion 2 Gy irradiation significantly inhibited the metastasis of tumor cells (p = 0.03). LC-MS analysis showed that 23 differential metabolites were obtained in the cell culture medium 24 h after carbon ion 0 and 2 Gy irradiation (9 up-regulated and 14 down-regulated). Among them, two were up-regulated and two down-regulated (p = 2.9 × 10−3). 41 target proteins were corresponding to these four differential molecules. Through the analysis of the KEGG signal pathway, it was found that these target molecules were mainly enriched in purine metabolism, tyrosine metabolism, cysteine and methionine metabolism, peroxisome, and carbon metabolism. Neuroactive ligand-receptor interaction, calcium signaling pathway, arachidonic acid metabolism, and Fc epsilon RI signaling pathway.ConclusionThe bystander effect induced by 2 Gy carbon ion radiation inhibits the metastasis of tumor cells, which indicates that carbon ions may change the metabolites of irradiated cells, so that it may indirectly affect the metabolism of tumor cell growth microenvironment, thus inhibiting the metastasis of malignant tumor cells.

Carbon Ion Radiotherapy Induce Metabolic Inhibition After Functional Imaging-Guided Simultaneous Integrated Boost for Prostate Cancer

“…Purine metabolites were increased in RTresistant cell lines when DNA damage occurred (52) after photon irradiation and the inhibition of de novo purine synthesis impairs DNA reparation (53) after irradiation. Alternation of purine metabolism could also be observed after carbon ion irradiation (54). In our research, several metabolites in purine metabolism were significantly discriminative between the two groups.…”

Remodeling of Chromatin Accessibility Regulates the Radiological Responses of NSCLC A549 Cells to High-LET Carbon Ions

“…As shown in Fig. 3B, these changed genes induced by carbon-ion irradiation were enriched in the p53 signaling pathway and metabolism-related pathways, which correlate with carbon-ion-induced radiation sensitivity ( 38 , 39 ). These findings suggest that the biological effects induced by carbon-ion irradiation of different LET are closely correlated with chromatin accessibility and gene transcription.…”

“…The interaction between CDK1 and p53 has been studied ( 54 ), but our data are able to explain from a chromatin accessibility perspective how carbon ions alter CDK1 transcript levels and influence the p53 signaling pathway. In addition, metabolomic analysis revealed that differential metabolites were enriched in the purine metabolic pathway 24 h after carbon-ion irradiation ( 39 ). We also found that genes regulated by chromatin accessibility were enriched in purine metabolism after irradiation with 50 keV/µm carbon ions, which was consistent with previous reports.…”

Long-Term Cardiac Damage Associated With Abdominal Irradiation in Mice

“…It could be the bystander effect of radiotherapy, that is, the same effect of radiotherapy on cells, tissues or organs in non-irradiated areas ( Wang et al, 2015 ; Fu et al, 2020 ). After irradiation, cells in the irradiated area can secrete cytokines, small molecular metabolites, exosomes or microvesicles containing various substances, and other media ( Lin et al, 2017 ; Ariyoshi et al, 2019 ; Ni et al, 2020 ; Mukherjee et al, 2021 ), resulting in metabolic disorders, apoptosis, endoplasmic reticulum and golgi dysfunction of cells in non-irradiated areas ( Yakovlev, 2015 ; Jella et al, 2018 ; Mladenov et al, 2018 ; Dong et al, 2020 ; Heeran et al, 2021 ; Yang et al, 2021 ). Earlier studies reported elevated levels of CRP in circulating blood, and splenic cells exhibited enhanced levels of oxidative stress and increased apoptosis after cranial irradiation in rats ( El-Din et al, 2017 ).…”