Kobayashi Alisa, Hiroyama Yota, Mamiya Taisei, Oikawa Masakazu, Konishi Teruaki
Single Cell Radiation Biology Team, National Institutes for Quantum Science and Technology, 4-9-1 Anagawa, Inageku, Chiba 263-8555, Japan.
Radiation Effect Research Group, Department of Accelerator and Medical Physics, National Institutes for Quantum Science and Technology, 4-9-1 Anagawa, Inageku, Chiba 263-8555, Japan.
Biology (Basel). 2023 Oct 25;12(11):1368. doi: 10.3390/biology12111368.
This study aimed to determine the mechanism underlying the modulation of radiosensitivity in cancer cells by the radiation-induced bystander effect (RIBE). We hypothesized that the RIBE mediates cyclooxygenase-2 (COX-2) and its metabolite prostaglandin E2 (PGE2) in elevating radioresistance in unirradiated cells. In this study, we used the SPICE-QST microbeam irradiation system to target 0.07-0.7% cells by 3.4-MeV proton microbeam in the cell culture sample, such that most cells in the dish became bystander cells. Twenty-four hours after irradiation, we observed COX-2 protein upregulation in microbeam-irradiated cells compared to that of controls. Additionally, 0.29% of the microbeam-irradiated cells exhibited increased cell survival and a reduced micronucleus rate against X-ray irradiation compared to that of non-microbeam irradiated cells. The radioresistance response was diminished in both cell groups with the hemichannel inhibitor and in COX-2-knockout cells under cell-to-cell contact and sparsely distributed conditions. The results indicate that the RIBE upregulates the cell radioresistance through COX-2/PGE2 intercellular responses, thereby contributing to issues, such as the risk of cancer recurrence.
本研究旨在确定辐射诱导旁观者效应（RIBE）调节癌细胞放射敏感性的潜在机制。我们假设RIBE通过环氧合酶-2（COX-2）及其代谢产物前列腺素E2（PGE2）介导未受照射细胞放射抗性的升高。在本研究中，我们使用SPICE-QST微束照射系统，通过3.4 MeV质子微束靶向细胞培养样本中0.07 - 0.7%的细胞，使培养皿中的大多数细胞成为旁观者细胞。照射后24小时，与对照组相比，我们观察到微束照射细胞中COX-2蛋白上调。此外，与未进行微束照射的细胞相比，0.29%的微束照射细胞对X射线照射表现出细胞存活率增加和微核率降低。在细胞间接触和稀疏分布条件下，半通道抑制剂处理的两个细胞组以及COX-2基因敲除细胞中的放射抗性反应均减弱。结果表明，RIBE通过COX-2/PGE2细胞间反应上调细胞放射抗性，从而导致癌症复发风险等问题。
