Effects of carbon‐ion beam irradiation on the angiogenic response in lung adenocarcinoma A549 cells

Liu, Yuanyuan; Liu, Yang; Zhang, Hong; Sun, Chao; Zhao, Qiuyue; Di, Cixia; Li, Hongyan; Gan, Lu; Wang, Yali

doi:10.1002/cbin.10327

Cited by 9 publications

(6 citation statements)

References 23 publications

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“…In the present study, there was no notable difference in the expression of VEGF in Tca8113 cells irradiated with X-rays compared with non-irradiated cells. By contrast, VEGF levels significantly decreased in cells irradiated with carbon ions compared with non-irradiated cells supporting the results of a previous study by Liu et al (37), who reported that carbon ion radiation decreased VEGF secretion in lung adenocarcinoma A549 cells. As the immunofluorescence assay can only show the location of the target protein and cannot detect the molecular weight of the protein, the effect of irradiation on VEGF expression needs to be confirmed using western blot analysis in future experiments.…”

Section: Discussionsupporting

confidence: 90%

Heavy‑ion beam irradiation inhibits invasion of tongue squamous cell carcinoma Tca8113 cells

Feng

Zheng

et al. 2019

Oncol Lett

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Tongue squamous cell carcinoma (TSCC) is a common malignant tumor type with aggressive biological characteristics, located in the oral and maxillofacial region. Vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) have been implicated in the invasion and metastasis of various malignant tumor types, such as lung cancer and gastric carcinoma. High linear energy transfer (LET) particle irradiation has several advantages over conventional X-rays in suppressing the invasion and metastasis of malignant tumors. The objective of the present study was to investigate the effects of high-LET carbon ions and low-LET X-rays on the expression of VEGF and MMPs, and to identify the associated mechanisms in the Tca8113 TSCC cell line. Tca8113 cells were irradiated with carbon ions or X-rays at doses of 1 and 4 Gy. An immunofluorescence assay indicated that VEGF expression was notably decreased at 24 and 48 h after heavy ion irradiation compared with irradiation with conventional X-rays. The expression of MMP-2 and MMP-9 also decreased in a dose-dependent manner following heavy ion irradiation. These findings indicate that compared with low-LET X-ray irradiation, high-LET carbon ions possess higher biological efficacy in inhibiting the invasive ability of Tca8113 cells via reduction of VEGF, MMP-2 and MMP-9 expression.

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Section: Discussionsupporting

confidence: 90%

Heavy‑ion beam irradiation inhibits invasion of tongue squamous cell carcinoma Tca8113 cells

Feng

Zheng

et al. 2019

Oncol Lett

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“…Conventional radiotherapy using gamma rays or X-rays is facing various difficulties like it lacks dose-localization to the target tumor cells, it grows radio-resistance, it is not effective for hypoxic tumors or deep seated tumors and importantly it triggers cancer metastasis by activating matrix metalloproteinases in various cancer cell-types as discussed in the Background section. On the contrary, high LET radiation or charged particles like carbon ion has better potential to suppress metastatic nature of cancer cells in vitro and in vivo [ 56 , 57 ] including its other beneficial roles over low LET radiations as described earlier. But the detailed mechanism is not clear.…”

Section: Discussionmentioning

confidence: 99%

PARP-1 depletion in combination with carbon ion exposure significantly reduces MMPs activity and overall increases TIMPs expression in cultured HeLa cells

et al. 2016

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BackgroundHadron therapy is an innovative technique where cancer cells are precisely killed leaving surrounding healthy cells least affected by high linear energy transfer (LET) radiation like carbon ion beam. Anti-metastatic effect of carbon ion exposure attracts investigators into the field of hadron biology, although details remain poor. Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors are well-known radiosensitizer and several PARP-1 inhibitors are in clinical trial. Our previous studies showed that PARP-1 depletion makes the cells more radiosensitive towards carbon ion than gamma. The purpose of the present study was to investigate combining effects of PARP-1 inhibition with carbon ion exposure to control metastatic properties in HeLa cells.MethodsActivities of matrix metalloproteinases-2, 9 (MMP-2, MMP-9) were measured using the gelatin zymography after 85 MeV carbon ion exposure or gamma irradiation (0- 4 Gy) to compare metastatic potential between PARP-1 knock down (HsiI) and control cells (H-vector - HeLa transfected with vector without shRNA construct). Expression of MMP-2, MMP-9, tissue inhibitor of MMPs such as TIMP-1, TIMP-2 and TIMP-3 were checked by immunofluorescence and western blot. Cell death by trypan blue, apoptosis and autophagy induction were studied after carbon ion exposure in each cell-type. The data was analyzed using one way ANOVA and 2-tailed paired-samples T-test.ResultsPARP-1 silencing significantly reduced MMP-2 and MMP-9 activities and carbon ion exposure further diminished their activities to less than 3 % of control H-vector. On the contrary, gamma radiation enhanced both MMP-2 and MMP-9 activities in H-vector but not in HsiI cells. The expression of MMP-2 and MMP-9 in H-vector and HsiI showed different pattern after carbon ion exposure. All three TIMPs were increased in HsiI, whereas only TIMP-1 was up-regulated in H-vector after irradiation. Notably, the expressions of all TIMPs were significantly higher in HsiI than H-vector at 4 Gy. Apoptosis was the predominant mode of cell death and no autophagic death was observed.ConclusionsOur study demonstrates for the first time that PARP-1 inhibition in combination with carbon ion synergistically decreases MMPs activity along with overall increase of TIMPs. These data open up the possibilities of improvement of carbon ion therapy with PARP-1 inhibition to control highly metastatic cancers.Electronic supplementary materialThe online version of this article (doi:10.1186/s13014-016-0703-x) contains supplementary material, which is available to authorized users.

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“…Some pro-inflammatory and pro-angiogenic genes, such as CCL2 , CSF1 , IL8 and PDGFB , seemed to be overexpressed by the co-culture configuration no matter if the cells were irradiated or not. It is however interesting to note that two studies reported angiogenic suppressive effects after irradiation of cancer cells with protons [ 34 ] or carbon ions [ 35 ]. In EC, CCL5 , IL8 and CXCL10 genes were overexpressed independently of irradiation and PDGFB and CSF1 gene overexpression had also similar profile to the one of FAS .…”

Section: Discussionmentioning

confidence: 99%

Effects of Alpha Particle and Proton Beam Irradiation as Putative Cross-Talk between A549 Cancer Cells and the Endothelial Cells in a Co-Culture System

Riquier

Abel

Wera

et al. 2015

Cancers

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Background: High-LET ion irradiation is being more and more often used to control tumors in patients. Given that tumors are now considered as complex organs composed of multiple cell types that can influence radiosensitivity, we investigated the effects of proton and alpha particle irradiation on the possible radioprotective cross-talk between cancer and endothelial cells. Materials and Methods: We designed new irradiation chambers that allow co-culture study of cells irradiated with a particle beam. A549 lung carcinoma cells and endothelial cells (EC) were exposed to 1.5 Gy of proton beam or 1 and 2 Gy of alpha particles. Cell responses were studied by clonogenic assays and cell cycle was analyzed by flow cytometry. Gene expression studies were performed using Taqman low density array and by RT-qPCR. Results: A549 cells and EC displayed similar survival fraction and they had similar cell cycle distribution when irradiated alone or in co-culture. Both types of irradiation induced the overexpression of genes involved in cell growth, inflammation and angiogenesis. Conclusions: We set up new irradiation chamber in which two cell types were irradiated together with a particle beam. We could not show that tumor cells and endothelial cells were able to protect each other from particle irradiation. Gene expression changes were observed after particle irradiation that could suggest a possible radioprotective inter-cellular communication between the two cell types but further investigations are needed to confirm these results.

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Effects of carbon‐ion beam irradiation on the angiogenic response in lung adenocarcinoma A549 cells

Cited by 9 publications

References 23 publications

Heavy‑ion beam irradiation inhibits invasion of tongue squamous cell carcinoma Tca8113 cells

Heavy‑ion beam irradiation inhibits invasion of tongue squamous cell carcinoma Tca8113 cells

PARP-1 depletion in combination with carbon ion exposure significantly reduces MMPs activity and overall increases TIMPs expression in cultured HeLa cells

Effects of Alpha Particle and Proton Beam Irradiation as Putative Cross-Talk between A549 Cancer Cells and the Endothelial Cells in a Co-Culture System

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