Imamichi Shoji, Chen Lichao, Ito Tasuku, Tong Ying, Onodera Takae, Sasaki Yuka, Nakamura Satoshi, Mauri PierLuigi, Sanada Yu, Igaki Hiroshi, Murakami Yasufumi, Suzuki Minoru, Itami Jun, Masunaga Shinichiro, Masutani Mitsuko
Department of Molecular and Genomic Biomedicine, School of Biomedical Sciences, Nagasaki University Graduate, Nagasaki 852-8523, Japan.
Lab of Collaborative Research, Division of Cellular Signaling, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Biology (Basel). 2022 Mar 10;11(3):420. doi: 10.3390/biology11030420.
Boron neutron capture therapy (BNCT) is a non-invasive therapeutic technique for treating malignant tumors, however, methods to evaluate its therapeutic efficacy and adverse reactions are lacking. High mobility group box 1 (HMGB1) is an inflammatory molecule released during cell death. Therefore, we aimed to investigate HMGB1 as a biomarker for BNCT response, by examining the early responses of tumor cells to B-boronophenylalanine (BPA)-based BNCT in the Kyoto University Nuclear Reactor. Extracellular HMGB1 release was significantly increased in human squamous carcinoma SAS and melanoma A375 cells 24 h after neutron irradiation but not after γ-irradiation. At 3 days post-BPA-based BNCT irradiation in a SAS xenograft mouse model, plasma HMGB1 levels were higher than those in the non-irradiation control, and HMGB1 was detected in both nuclei and cytoplasm in tumor cells. Additionally, increased plasma HMGB1 levels post-BNCT irradiation were detected even when tumors decreased in size. Collectively, these results indicate that the extracellular HMGB1 release occurs at an early stage and is persistent when tumors are reduced in size; therefore, it is a potential biomarker for evaluating the therapeutic response during BNCT.
硼中子俘获疗法（BNCT）是一种用于治疗恶性肿瘤的非侵入性治疗技术，然而，目前缺乏评估其治疗效果和不良反应的方法。高迁移率族蛋白B1（HMGB1）是细胞死亡过程中释放的一种炎症分子。因此，我们旨在通过研究肿瘤细胞对基于B-硼苯丙氨酸（BPA）的BNCT在京都大学核反应堆中的早期反应，来探究HMGB1作为BNCT反应生物标志物的可能性。中子照射后24小时，人鳞状细胞癌SAS细胞和黑色素瘤A375细胞的细胞外HMGB1释放显著增加，但γ射线照射后未增加。在基于BPA的BNCT照射后3天，SAS异种移植小鼠模型中的血浆HMGB1水平高于未照射对照组，并且在肿瘤细胞的细胞核和细胞质中均检测到HMGB1。此外，即使肿瘤体积缩小，BNCT照射后血浆HMGB1水平仍会升高。总体而言，这些结果表明，细胞外HMGB1释放在早期阶段发生，并且在肿瘤体积缩小时持续存在；因此，它是评估BNCT治疗反应的潜在生物标志物。
