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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

机译:共培养系统中α粒子和质子束辐射作为A549癌细胞与内皮细胞之间的交叉对话的影响

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摘要

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.
机译:背景:高LET离子辐射正越来越多地用于控制患者的肿瘤。鉴于现在将肿瘤视为由多种细胞类型组成的复杂器官,这些细胞类型可能会影响放射敏感性,因此我们研究了质子和α粒子辐照对癌症与内皮细胞之间可能的放射防护串扰的影响。材料和方法:我们设计了新的辐照室,可以对用粒子束辐照的细胞进行共培养研究。将A549肺癌细胞和内皮细胞(EC)暴露于1.5 Gy的质子束或1和2 Gy的α粒子。通过克隆形成测定研究细胞应答,并通过流式细胞术分析细胞周期。使用Taqman低密度阵列和RT-qPCR进行基因表达研究。结果:单独或联合培养时,A549细胞和EC表现出相似的存活率,并且具有相似的细胞周期分布。两种类型的辐射均诱导涉及细胞生长,炎症和血管生成的基因的过表达。结论:我们建立了一个新的辐照室,在该辐照室中用粒子束辐照了两种细胞。我们不能证明肿瘤细胞和内皮细胞能够相互保护免受微粒辐射。粒子辐照后观察到基因表达变化,这可能表明两种细胞类型之间可能存在辐射防护性细胞间通讯,但需要进一步研究以证实这些结果。

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