Effects Of Carbon Ion Irradiation Research Articles

Combined effects of carbon ion radiation and PARP inhibitor on non-small cell lung carcinoma cells: Insights into DNA repair pathways and cell death mechanisms

The utilization of high linear energy transfer (LET) carbon ion (12C-ion) in radiotherapy has witnessed a notable rise in managing highly metastatic, recurrent, and chemo/radio-resistant human cancers. Non-small cell lung cancer (NSCLC) presents a formidable challenge due to its chemo-resistance and aggressive nature, resulting in poor prognosis and survival rates. In a previous study, we demonstrated that the combination of 12C-ion with the poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) olaparib significantly mitigated metastasis in A549 cells. Here, we delve into the underlying rationale behind the combined action of olaparib with 12C-ion, focusing on DNA repair pathways and cell death mechanisms in asynchronous NSCLC A549 cells following single and combined treatments. Evaluation included analysis of colony-forming ability, DNA damage assessed by γH2AX foci, expression profiling of key proteins involved in Homologous Recombination (HR) and Non-Homologous End Joining (NHEJ) repair pathways, caspase-3 activation, apoptotic body formation, and autophagic cell death. Our findings reveal that both PARPi olaparib and rucaparib sensitize A549 cells to 12C-ion exposure, with olaparib exhibiting superior sensitization. Moreover, 12C-ion exposure alone significantly downregulates both HR and NHEJ repair pathways by reducing the expression of MRE11--RAD51 and Ku70-Ku80 protein complexes at 24 h post-treatment. Notably, the combination of olaparib pre-treatment with 12C-ion markedly inhibits both HR and NHEJ pathways, culminating in DNA damage-induced apoptotic and autophagic cell death. Thus we are the first to demonstrate that olaparib sensitizes NSCLC cells to carbon ion by interfering with HR and NHEJ pathway. These insights underscore the promising therapeutic potential of combining PARP inhibition with carbon ion exposure for effective NSCLC management.

Carbon ion irradiation exerts antitumor activity by inducing cGAS-STING activation and immune response in prostate cancer-bearing mice.

As an advanced radiotherapy technique, carbon ion radiotherapy has demonstrated good efficacy and low toxicity for prostate cancer patients, but the radiobiological mechanism of killing tumor cells has not been fully elucidated. This study aims to explore the antitumor effects of carbon ion irradiation (CIR) through investigating the immune response induced by CIR in prostate cancer-bearing mice and the underlying molecular mechanism. We established subcutaneous transplantation tumor models of prostate cancer to evaluate the tumor inhibition effect of CIR. Investigation of immunophenotype alterations were assessed by flow cytometry. Immunofluorescence, western blot, and real-time quantitative PCR was employed to analyze the activation of cGAS-STING pathway. CIR showed more powerful tumor growth control than photon irradiation in immunocompetent syngeneic C57BL/6 mice. CIR exerts antitumor effect by triggering immune response, characterized by increased CD4+ T cells and macrophages in tumor, enhanced CD8+ T cells and T effector memory cells in spleen, improved IFN-γ production of CD8+ tumor-infiltrating lymphocytes, and reduced exhausted T cells in tumor and spleen. Additionally, production of cytoplasmic double-stranded DNA, protein levels of p-TBK1 and p-IRF3 in the cGAS-STING pathway, and gene expression levels of downstream interferon-stimulated genes were significantly increased after CIR in a dose-dependent manner. Treatment of RM1 tumor-bearing mice with the STING inhibitor C-176 impaired the antitumor effect of CIR. The excellent antitumor activity of CIR in immunocompetent prostate cancer-bearing C57BL/6 mice may be attributed to stronger induction of antitumor immune response and higher activation of cGAS-STING pathway.

Silencing of Fused Toes Homolog (FTS) Increases Radiosensitivity to Carbon-Ion Through Downregulation of Notch Signaling in Cervical Cancer Cells.

The effects of Carbon ion radiation (C-ion) alone or in combination with fused toes homolog (FTS) silencing on Notch signaling were investigated in uterine cervical cancer cell lines (ME180 and CaSki). In both cell lines, upon irradiation with C-ion, the expression of Notch signaling molecules (Notch1, 2, 3 and cleaved Notch1), γ-secretase complex molecules and FTS was upregulated dose-dependently (1, 2 and 4 Gy) except Notch1 in ME180 cells where the change in expression was not significant. However, overexpression of these molecules was attenuated upon silencing of FTS. The spheroid formation, expression of stem cell markers (OCT4A, Sox2 and Nanog) and clonogenic cell survival were reduced by the combination as compared to FTS silencing or C-ion irradiation alone. Additionally, immunoprecipitation and immunofluorescence assay revealed interaction and co-localization of FTS with Notch signaling molecules. In conclusion, FTS silencing enhances the radio-sensitivity of the cervical cancer cells to C-ion by downregulating Notch signaling molecules and decreasing the survival of cancer stem cells.

Carbon ion irradiation-induced DNA damage evokes cell cycle arrest and apoptosis via the pRb/E2F1/c-Myc signaling pathway in p53-deficient prostate cancer PC-3 cells

Carbon ion radiotherapy has the advantages of better therapeutic effect and fewer side effects compared with those of X-rays in many kinds of tumors, including prostate cancer, and thus is an attractive treatment approach for prostate cancer. However, the biological effects and underlying mechanisms of carbon ion irradiation in prostate cancer are not yet fully understood. Therefore, this study systematically compared the effects of carbon ion irradiation with those of X-ray irradiation on DNA damage response and found that carbon ion irradiation was more effective than X-ray irradiation. Carbon ion irradiation can induce a high level of DNA double-strand break damage, reflected by the number of γ-H2A histone family member X foci, as well as by the foci lasting time and size. Moreover, carbon ion irradiation exhibited strong and long-lasting inhibitory effect on cell survival capability, induced prolonged cell cycle arrest, and increased apoptosis in PC-3 cells. As an underlying mechanism, we speculated that carbon ion irradiation-induced DNA damage evokes cell cycle arrest and apoptosis via the pRb/E2F1/c-Myc signaling pathway to enhance the radiosensitivity of p53-deficient prostate cancer PC-3 cells. Collectively, the present study suggests that carbon ion irradiation is more efficient than X-ray irradiation and may help to understand the effects of different radiation qualities on the survival potential of p53-deficient prostate cancer cells.

Photon versus carbon ion irradiation: immunomodulatory effects exerted on murine tumor cell lines

While for photon radiation hypofractionation has been reported to induce enhanced immunomodulatory effects, little is known about the immunomodulatory potential of carbon ion radiotherapy (CIRT). We thus compared the radio-immunogenic effects of photon and carbon ion irradiation on two murine cancer cell lines of different tumor entities. We first calculated the biological equivalent doses of carbon ions corresponding to photon doses of 1, 3, 5, and 10 Gy of the murine breast cancer cell line EO771 and the OVA-expressing pancreatic cancer cell line PDA30364/OVA by clonogenic survival assays. We compared the potential of photon and carbon ion radiation to induce cell cycle arrest, altered surface expression of immunomodulatory molecules and changes in the susceptibility of cancer cells to cytotoxic T cell (CTL) mediated killing. Irradiation induced a dose-dependent G2/M arrest in both cell lines irrespective from the irradiation source applied. Likewise, surface expression of the immunomodulatory molecules PD-L1, CD73, H2-Db and H2-Kb was increased in a dose-dependent manner. Both radiation modalities enhanced the susceptibility of tumor cells to CTL lysis, which was more pronounced in EO771/Luci/OVA cells than in PDA30364/OVA cells. Overall, compared to photon radiation, the effects of carbon ion radiation appeared to be enhanced at higher dose range for EO771 cells and extenuated at lower dose range for PDA30364/OVA cells. Our data show for the first time that equivalent doses of carbon ion and photon irradiation exert similar immunomodulating effects on the cell lines of both tumor entities, highlighted by an enhanced susceptibility to CTL mediated cytolysis in vitro.

Evaluation of 8.0 MeV Carbon (C2+) Irradiation Effects on Hydrothermally Synthesized Co3O4−CuO−ZnO@GO Electrodes for Supercapacitor Applications

AbstractCombination of transition metal oxides and carbon derivatives have received a lot of interest in last two decades for electrochemical energy storage due to their small size and high specific surface area. The effects of carbon ion irradiation on the properties of the electrodes were examined. The structural properties as obtained from the X‐ray diffraction (XRD) results suggest that irradiation of the nanocomposite enhances the crystallinity of the materials up to the optimal dose of 5.0×1015 ions/cm2. Beyond this dose, there was a reduction in the crystallinity occasioned by distortion and defects in the structure of the material. The morphological studies indicated that the nanocomposites have spherical nanoparticles with some agglomerations. The agglomerations as well the particle sizes reduced with increase in the radiation dosages. The energy bandgaps estimated for the Co3O4−CuO−ZnO@GO reduced as energy dosages increases. The highest specific capacitance obtained from cyclic voltammetry (CV) plots at 10 mV/s scan rate and galvanostatic charge‐discharge (GCD) were 1950 and 2045 F/g at a radiation dose of 5.0×1015 ions/cm2. Results indicate that carbon ion irradiations, especially low doses enhance the characteristics performance of these electrodes while high doses induce deficiencies and disorder to the Co3O4−CuO−ZnO@GO electrodes. These results also indicate that radiation is a useful tool to enhance or damage properties of nanomaterials especially with low energy doses.

Effect of carbon ion irradiation on the structural, mechanical and electrical properties of polycrystalline tungsten

To investigate the effects of carbon ion irradiation on the structural, mechanical and electrical properties of polycrystalline tungsten, four tungsten specimens were irradiated by 5 MeV carbon ions (C+2) at various doses ranging from 0.5 × 1015 to 3 × 1015 ions cm−2 for different exposure times. X-ray diffraction analysis confirmed the slight structural modification by increase or decrease in diffracted peak intensity, crystallite size and lattice strains upon ion irradiation. In addition, there was no substantial evidence of new phase/s in α-tungsten at high energy ions. Initially, at a lower dose rate of 0.5 × 1015 ions cm−2, the average surface hardness and electrical resistivity were found to decrease due to the increase of crystallite size. However, elevated dosed (≥1 × 1015 ions cm−2) specimens show a significant increase in their surface hardness and electrical resistivity in comparison to un-irradiated ones. The variation of surface hardness and electrical resistivity of irradiated tungsten is well correlated with crystallographic modifications, which is ascribed to the generation, recombination, augmentation, and annihilation of ion-induced defects.

DNA damage response of clinical carbon ion versus photon radiation in human glioblastoma cells

Background and purposeCarbon ion radiotherapy is a promising therapeutic option for glioblastoma patients due to its high physical dose conformity and greater biological effectiveness than photons. However, the biological effects of carbon ion radiation are still incompletely understood. Here, we systematically compared the biological effects of clinically used carbon ion radiation to photon radiation with emphasis on DNA repair. Materials and methodsTwo human glioblastoma cell lines (U87 and LN229) were irradiated with carbon ions or photons and DNA damage response was systematically analyzed, including clonogenic survival, induction and repair of DNA double-strand breaks (DSBs), cell cycle arrest and apoptosis or autophagy. γH2AX foci were analyzed by flow cytometry, conventional light microscopy and 3D superresolution microscopy. ResultsDSBs were repaired delayed and with slower kinetics after carbon ions versus photons. Carbon ions caused stronger and longer-lasting cell cycle delays, predominantly in G2 phase, and a higher rate of apoptosis. Compared to photons, the effectiveness of carbon ions was less cell cycle-dependent. Homologous recombination (HR) appeared to be more important for DSB repair after carbon ions versus photons in phosphatase and tensin homolog (PTEN)-deficient U87 cells, as opposed to PTEN-proficient LN229 cells. ConclusionCarbon ions induced more severe DSB damage than photons, which was repaired less efficiently in both cell lines. Thus, carbon ion radiotherapy may help to overcome resistance mechanisms of glioblastoma associated with DNA repair for example in combination with repair pathway-specific drugs in the context of personalized radiotherapy.

The Potential Application of Heavy Ion Beams in the Treatment of Arrhythmia: The Role of Radiation-Induced Modulation of Connexin43 and the Sympathetic Nervous System.

It has been known that heart disease-such as myocardial infarction (MI), cardiac hypertrophy, or heart failure-alters the molecular structure and function of the gap junction, which can lead to an abnormal heart rhythm. Radiation has been shown to modulate intercellular communication in the skin and lungs by increasing connexin43 (Cx43) expression. Understanding how Cx43 upregulation is induced in a diseased heart can help provide a new perspective to radiation therapy for arrhythmias. In a recent study with rabbits after MI, carbon ions were accelerated to 290 MeV/u and extracted in the air; a biologically (cell kill) uniform 6-cm spread-out Bragg peak beam was generated, and beam tissue depth was set to 30 mm with energy degraders to the depth position. Targeted heavy ion irradiation (THIR) with 15 Gy to the left ventricle increased Cx43 expression, improved conductivity, decreased the spatial heterogeneity of repolarization, and reduced the vulnerability of rabbit hearts to ventricular arrhythmias after MI. In clinically normal rabbits, THIR > = 10 Gy caused a significant dose-dependent increase of Cx43 protein and messenger RNA 2 weeks after irradiation. The left (irradiated) and right (nonirradiated) ventricles exhibited circumferential upregulation of Cx43 lasting for at least 1 year. There were no significant changes in electrocardiograms and echocardiograms, indicating no apparent injury for 1 year. A single exposure of 135 MeV/u THIR with 15 Gy to a dog heart attenuated vulnerability to ventricular arrhythmia after the induction of MI for at least 1 year through the modulation of Cx43 expression. This long-lasting remodeling effect on gap junctions may lay the groundwork to novel therapies against life-threatening ventricular arrhythmias in structural heart disease. To date, there have been few investigations into the effects of carbon-ion irradiation on electrophysiological properties in the human heart. Patients with mediastinum cancer were investigated for 5 years after treatment that included irradiation to the heart, and investigators found that carbon-ion beam irradiation to the heart is not immediately cardiotoxic and demonstrates consistent signals of arrhythmia reduction. Its practical application in non-cancer treatment, such as in arrhythmia treatment, is highly anticipated.

Effects of 12C6+ Heavy Ion Radiation on Dendritic Cells Function.

BackgroundCarbon ion radiotherapy has been shown to be more effective in cancer radiotherapy than photon irradiation. Influence of carbon ion radiation on cancer microenvironment is very important for the outcomes of radiotherapy. Tumor-infiltrating dendritic cells (DCs) play critical roles in cancer antigen processing and antitumor immunity. However, there is scant literature covering the effects of carbon ion radiation on DCs. In this study, we aimed to uncover the impact of carbon ion irradiation on bone marrow derived DCs.Material/MethodsBone marrow cells were co-cultured with GM-CSF and IL-4 for seven days, and the population of DCs was confirmed with flow cytometry. We used an Annexin V and PI staining method to detect cell apoptosis. Endocytosis assay of DCs was determined by using a flow cytometry method. DCs migration capacity was tested by a Transwell method. We also used ELISA assay and western blotting assay to examine the cytokines and protein expression, respectively.ResultsOur data showed that carbon ion radiation induced apoptosis in both immature and mature DCs. After irradiation, the endocytosis and migration capacity of DCs was also impaired. Interestingly, carbon irradiation triggered a burst of IFN-γ and IL-12 in LPS or CpG treated DCs, which provide novel insights into the combination of immunotherapy and carbon ion radiotherapy. Finally, we found that carbon ion irradiation induced apoptosis and migration suppression was p38 dependent.ConclusionsOur present study demonstrated that carbon ion irradiation induced apoptosis in DCs, and impaired DCs function mainly through the p38 signaling pathway. Carbon ion irradiation also triggered anti-tumor cytokines secretion. This work provides novel information of carbon ion radiotherapy in DCs, and also provides new insights on the combination of immune adjuvant and carbon ion radiotherapy.

A New Approach for Quantifying Radio-Biological Effects Using the Time Course of Mouse Leg Contracture.

A digitization approach to the time course of radiation-induced mouse leg contracture was proposed for quantifying the radiation effect on an individual living mouse. The shortening of the mouse leg length can be easily measured with a caliper/ruler to offer a very simple digitalized index of the radiation effect. Left hind legs of mice were irradiated with single dose of 32 Gy of 290 MeV carbon-ion beam using 0, 50, or 117 mm binary filter (BF). The right legs were used as a control. The lengths of both hind legs of the mice were measured using a digital caliper before irradiation and every week after irradiation. The degree of leg contracture, ΔSt, at the time point t was estimated by subtraction of the left irradiated leg length from the right control leg length. Equation was fitted on the daily time course of ΔSt, and two parameters, ΔSmax and Ts, were estimated. ΔSt=ΔSmax×(1-exp(t/Ts)), where ΔSmax is the maximum degree of leg contracture, and Ts is time of leg contracture. The effect of carbon-ion irradiation on a living mouse was quantified by ΔSmax and Ts of the leg contracture, and then compared to that of X-rays. By 32 Gy irradiation, ΔSmax was largest for the BF117 experiment, followed by X-ray~BF50>BF0. Ts was shortest for the BF50 experiment, while other irradiation conditions give similar Ts. A logarithmic function was successfully repurposed for the evaluation of radio-biological response.

Changes in arrhythmogenic properties and five-year prognosis after carbon-ion radiotherapy in patients with mediastinum cancer.

Carbon-ion irradiation of rabbit hearts has improved left ventricular conduction abnormalities through upregulation of gap junctions. However, to date, there has been no investigation on the effect of carbon-ion irradiation on electrophysiological properties in human. We investigated this effect in patients with mediastinum extra-cardiac cancer treated with carbon-ion radiotherapy that included irradiating the heart. In April-December 2009, eight patients were prospectively enrolled (including two male, aged 72.5±13.0years). They were treated with 44-72 Gray equivalent (GyE), with their hearts exposed to 1.3-19.1 GyE. High-resolution ambulatory electrocardiography was performed before and after radiotherapy to investigate arrhythmic events, late potentials (LPs), and heart rate variability. Five patients had pre-existing premature ventricular contraction (PVC)/atrial contraction (PAC) or paroxysmal atrial fibrillation (PAF)/AF; after irradiation, this improved in four patients with PVC/PAF/AF and did not deteriorate in one patient with PAC. Ventricular LP findings did not deteriorate and improved in one patient. In eight cases with available atrial LP findings, there was no deterioration, and two patients showed improvements. The low frequency/high frequency ratio of heart rate variability improved or did not deteriorate in the six patients who received radiation exposure to the bilateral stellate ganglions. During the five-year follow-up for the prognosis, six of the eight patients died because of cancer; there was no history of hospitalization for cardiac events. Although this preliminary study has several limitations, carbon-ion beam irradiation to the heart is not immediately cardiotoxic and demonstrates consistent signals of arrhythmia reduction.

Histone Deacetylase Inhibitors Sensitize Murine B16F10 Melanoma Cells to Carbon Ion Irradiation by Inducing G1 Phase Arrest.

Epigenetic processes, in addition to genetic abnormalities, play a critical role in refractory malignant diseases and cause the unresponsiveness to various chemotherapeutic regimens and radiotherapy. Herein we demonstrate that histone deacetylase inhibitors (HDACis) can be used to sensitize malignant melanoma B16F10 cells to carbon ion irradiation. The cells were first treated with HDACis (romidepsin [FK228, depsipeptide], trichostatin A [TSA], valproic acid [VPA], and suberanilohydroxamic acid [SAHA, vorinostat]) and were then exposed to two types of radiation (carbon ions and gamma-rays). We found that HDACis enhanced the radiation-induced apoptosis and suppression of clonogenicity that was induced by irradiation, having a greater effect with carbon ion irradiation than with gamma-rays. Carbon ion irradiation and the HDACi treatment induced G2/M and G0/G1 cell cycle arrest, respectively. Thus, it is considered that HDACi treatment enhanced the killing effects of carbon ion irradiation against melanoma cells by inducing the arrest of G1 phase cells, which are sensitive to radiation due to a lack of DNA homologous recombination repair. Based on these findings, we propose that pretreatment with HDACis as radiosensitizers to induce G1 arrest combined with carbon ion irradiation may have clinical efficacy against refractory cancer.

Telomere-Mitochondrion Links Contribute to Induction of Senescence in MCF-7 Cells after Carbon-Ion Irradiation.

The effects of carbon-ion irradiation on cancer cell telomere function have not been comprehensively studied. In our previous report cancer cells with telomere dysfunction were more sensitive to carbon-ion irradiation, but the underlying mechanisms remained unclear. Here we found that telomerase activity was suppressed by carbon-ion irradiation via hTERT down-regulation. Inhibition of telomere activity by MST-312 further increased cancer cell radiosensitivity to carbon-ion radiation. hTERT suppression caused by either carbon-ion irradiation or MST-312 impaired mitochondrial function, as indicated by decreased membrane potential, mtDNA copy number, mitochondrial mass, total ATP levels and elevated reactive oxygen species (ROS). PGC-1α expression was repressed after carbion-ion irradiation, and hTERT inhibition by MST-312 could further exacerbate this effect. Lowering the mitochondrial ROS level by MitoTEMPO could partially counteract the induction of cellular senescence induced by carbon-ion radiation and MST-312 incubation. Taken together, the current data suggest that telomere-mitochondrion links play a role in the induction of senescence in MCF-7 cells after carbon-ion irradiation.

Effects of carbon ion irradiation and X-ray irradiation on the ubiquitylated protein accumulation.

C-ion radiotherapy is associated with improved local control and survival in several types of tumors. Although C-ion irradiation is widely reported to effectively induce DNA damage in tumor cells, the effects of irradiation on proteins, such as protein stability or degradation in response to radiation stress, remain unknown. We aimed to compare the effects of C-ion and X-ray irradiation focusing on the cellular accumulation of ubiquitylated proteins. Cells from two human colorectal cancer cell lines, SW620 and SW480, were subjected to C-ion or X-ray irradiation and determination of ubiquitylated protein levels. High levels of ubiquitylated protein accumulation were observed in the C-ion-irradiated SW620 with a peak at 3 Gy; the accumulation was significantly lower in the X-ray-irradiated SW620 at all doses. Enhanced levels of ubiquitylated proteins were also detected in C-ion or X-ray-irradiated SW480, however, those levels were significantly lower than the peak detected in the C-ion-irradiated SW620. The levels of irradiation-induced ubiquitylated proteins decreased in a time-dependent manner, suggesting that the proteins were eliminated after irradiation. The treatment of C-ion-irradiated SW620 with a proteasome inhibitor (epoxomicin) enhanced the cell killing activity. The accumulated ubiquitylated proteins were co-localized with γ-H2AX, and with TP53BP1, in C-ion-irradiated SW620, indicating C-ion-induced ubiquitylated proteins may have some functions in the DNA repair system. Overall, we showed C-ion irradiation strongly induces the accumulation of ubiquitylated proteins in SW620. These characteristics may play a role in improving the therapeutic ratio of C-ion beams; blocking the clearance of ubiquitylated proteins may enhance sensitivity to C-ion radiation.

Effects of Carbon-Ion Irradiation on the Morphology and Growth in the Local Green Soybean 'Kamame' in Aomori Prefecture

Effects of Carbon-Ion Irradiation on the Morphology and Growth in the Local Green Soybean 'Kamame' in Aomori Prefecture

Effects of 12C6+ ion radiation and ferulic acid on the zebrafish (Danio rerio) embryonic oxidative stress response and gene expression

The effects of carbon ion irradiation and ferulic acid (FA) on the induction of oxidative stress and alteration of gene expression were studied in zebrafish (Danio rerio) embryos. Zebrafish embryos at 8 hpf were divided into seven groups: the control group; the 1Gy, 3Gy and 7Gy irradiation groups; and three FA-pre-treated irradiation groups. In the irradiated groups, a significant increase in the teratogenesis of the zebrafish embryos and oxidative stress was accompanied by increased malondialdehyde (MDA) content, decreased glutathione (GSH) content and alterations in antioxidant enzyme activities (such as catalase [CAT] and superoxide dismutase [SOD]). Moreover, the mRNA levels for Cu/Zn–sod, Mn–sod, cat and gpx, the genes encoding these antioxidant proteins, were altered significantly. However, the mRNA expression patterns were not in accordance with those of the antioxidant enzymes and were more sensitive under low-dose irradiation. In addition, we detected the mRNA expression of ucp-2 and bcl-2, which are located at the mitochondrial inner membrane and related to reactive oxidative species (ROS) production. In the irradiated groups, the mRNA level of ucp-2 was significantly increased, whereas the mRNA level of bcl-2 was significantly decreased. Supplementation with FA, an antioxidant, was better able to reduce the irradiation-induced oxidative damage marked by changes in mortality, morphology, antioxidant enzyme activities and the MDA and GSH content, as well as in the mRNA expression levels. Overall, this study provided helpful information about the transcriptional effects of irradiation to better understand the mechanism of carbon ion-induced oxidative stress and FA-induced radioprotective effects.

Carbon Ion Irradiation Inhibits Glioma Cell Migration Through Downregulation of Integrin Expression

To investigate the effect of carbon ion irradiation on glioma cell migration. U87 and Ln229 glioma cells were irradiated with photons and carbon ions. Migration was analyzed 24 h after irradiation. Fluorescence-activated cell sorting analysis was performed in order to quantify surface expression of integrins. Single photon doses of 2 Gy and 10 Gy enhanced α(ν)β(3) and α(ν)β(5) integrin expression and caused tumor cell hypermigration on both vitronectin (Vn) and fibronectin (Fn). Compared to integrin expression in unirradiated cells, carbon ion irradiation caused decreased integrin expression and inhibited cell migration on both Vn and Fn. Photon radiotherapy (RT) enhances the risk of tumor cell migration and subsequently promotes locoregional spread via photon induction of integrin expression. In contrast to photon RT, carbon ion RT causes decreased integrin expression and suppresses glioma cell migration on both Vn and Fn, thus promising improved local control.

Effect of Carbon Ion Irradiation on Human Papillomavirus (HPV) 16 Positive Cervical Keratinocytes

Effect of Carbon Ion Irradiation on Human Papillomavirus (HPV) 16 Positive Cervical Keratinocytes

Carbon Ion Irradiation Suppresses Metastatic Potential of Human Non-small Cell Lung Cancer A549 Cells through the Phosphatidylinositol-3-Kinase/Akt Signaling Pathway

We previously showed that carbon ion irradiation can inhibit the expression of the anillin (ANLN) gene, which is regulated by the activation of the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway associated with metastasis. The purpose of this study is to compare the effects of carbon ion irradiation on the PI3K/Akt signaling pathway to those of photon irradiation. Our study showed that carbon ion irradiation of human lung adenocarcinoma cells A549 decreased their invasion more effectively than photon irradiation did. We found that carbon ion irradiation reduced the nuclear localization of ANLN at lower dose, but did not affect its expression. Low-dose carbon ion irradiation also reduced the level of phosphorylated Akt compared to untreated controls, whereas photon irradiation did not. These results suggest that carbon ion irradiation effectively suppresses the metastatic potential of A549 cells by suppressing the PI3K/Akt signaling pathway.