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在三维培养中生长的人胶质母细胞瘤(U87)细胞对X射线和质子辐射表现出抗辐射性。

Human glioblastoma (U87) cells grown in 3D culture showed a radio-resistance to X-ray and proton radiation.

作者信息

Kartini Dea A, Karoon Pharewa, Malad Yuwadee, Tippayamontri Thititip, Sanghangthum Taweap, Talabnin Chutima, Kobdaj Chinorat

机构信息

School of Physics, Institute of Science, Suranaree University of Technology, Nakhon Ratchasima, 30000, Thailand.

Department of Radiological Technology and Medical Physics, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.

出版信息

Radiol Phys Technol. 2025 Jun 13. doi: 10.1007/s12194-025-00921-2.

DOI:10.1007/s12194-025-00921-2
PMID:40514601
Abstract

Glioblastoma multiforme is the most malignant brain tumor and is resistant to conventional radiotherapy. Proton radiotherapy utilizes accelerated proton beams to irradiate deep-seated tumors with minimum ionization in the entrance channel, thanks to its inverted dose profile. This work aims to investigate the response of human glioma (U87) cells cultured in a 3D culture after X-ray and proton irradiation. U87 cells have been cultured in 3D bio-phantom where cells were grown in Matrigel matrix inside a 96-well plate. The morphology of U87 cells in 3D culture has been observed for 48 h, and cells have grown in their natural shape. The response of cells in 3D bio-phantom was evaluated by exposing the cells to 6 MV X-ray and 70 MeV monoenergetic proton beams. Post-irradiation, the surviving cells were determined by a colony formation assay, and the survival curve of cells in 3D culture was compared with the cells grown in 2D monolayer culture. The response of cells in the 3D bio-phantom following X-ray and proton radiation demonstrated an increased survival fraction in the high-dose region than those in 2D monolayer. However, U87 cells showed more sensitivity towards proton irradiation compared to X-rays, regardless of the culture setup. Finally, we obtained the RBE value of 1.15 for cells in 3D bio-phantom and 1.29 for cells in 2D monolayer. Therefore, U87 cells grown in our 3D culture setup demonstrate radio-resistant behavior and exhibit higher sensitivity towards proton irradiation compared to X-ray irradiation in our clonogenic assay.

摘要

多形性胶质母细胞瘤是最恶性的脑肿瘤,对传统放疗具有抗性。质子放疗利用加速质子束,由于其剂量分布倒置,在入射通道中以最小电离作用照射深部肿瘤。这项工作旨在研究人胶质瘤(U87)细胞在X射线和质子照射后在三维培养中的反应。U87细胞在三维生物模型中培养,细胞在96孔板内的基质胶基质中生长。观察了三维培养中U87细胞的形态48小时,细胞以其自然形态生长。通过将细胞暴露于6兆伏X射线和70兆电子伏特单能质子束来评估三维生物模型中细胞的反应。照射后,通过集落形成试验确定存活细胞,并将三维培养中细胞的存活曲线与二维单层培养中生长的细胞进行比较。X射线和质子辐射后三维生物模型中细胞的反应表明,高剂量区域的存活分数高于二维单层培养中的细胞。然而,无论培养设置如何,U87细胞对质子照射的敏感性都高于X射线。最后,我们获得了三维生物模型中细胞的相对生物效应值为1.15,二维单层培养中细胞的相对生物效应值为1.29。因此,在我们的三维培养设置中生长的U87细胞表现出抗辐射行为,并且在我们的克隆形成试验中,与X射线照射相比,对质子照射表现出更高的敏感性。

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本文引用的文献

1
Micro-Vessels-Like 3D Scaffolds for Studying the Proton Radiobiology of Glioblastoma-Endothelial Cells Co-Culture Models.用于研究胶质母细胞瘤-内皮细胞共培养模型中质子放射生物学的类微血管 3D 支架。
Adv Healthc Mater. 2024 Mar;13(6):e2302988. doi: 10.1002/adhm.202302988. Epub 2023 Nov 27.
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3D Cell Models in Radiobiology: Improving the Predictive Value of In Vitro Research.3D 细胞模型在放射生物学中的应用:提高体外研究的预测价值。
Int J Mol Sci. 2023 Jun 25;24(13):10620. doi: 10.3390/ijms241310620.
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Comparison of Radiation Response between 2D and 3D Cell Culture Models of Different Human Cancer Cell Lines.
不同人癌细胞系的 2D 和 3D 细胞培养模型的辐射反应比较。
Cells. 2023 Jan 18;12(3):360. doi: 10.3390/cells12030360.
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Extracellular matrix stiffness mediates radiosensitivity in a 3D nasopharyngeal carcinoma model.细胞外基质硬度在三维鼻咽癌模型中介导放射敏感性。
Cancer Cell Int. 2022 Nov 19;22(1):364. doi: 10.1186/s12935-022-02787-5.
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3D high resolution clonogenic survival measurement of xrs-5 cells in low-dose region of carbon ion plans.Xrs-5 细胞在碳离子计划低剂量区的三维高分辨率集落存活测量。
Int J Radiat Biol. 2023;99(3):488-498. doi: 10.1080/09553002.2022.2110318. Epub 2022 Aug 15.
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Intercomparison of radiosensitization induced by gold and iron oxide nanoparticles in human glioblastoma cells irradiated by 6 MV photons.金和氧化铁纳米颗粒在 6 MV 光子照射下人神经胶质瘤细胞中诱导放射增敏的比较。
Sci Rep. 2022 Jun 10;12(1):9602. doi: 10.1038/s41598-022-13368-x.
7
Evaluation of Proton-Induced DNA Damage in 3D-Engineered Glioblastoma Microenvironments.评估三维工程脑胶质瘤微环境中的质子诱导 DNA 损伤。
ACS Appl Mater Interfaces. 2022 May 11;14(18):20778-20789. doi: 10.1021/acsami.2c03706. Epub 2022 Apr 20.
8
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