| Luo Yunbin,Zhang Jiaying,Lyu Jianfeng,et al.Short-term changes in energy metabolism of breast cancer cells under ultra-high dose rate irradiation[J].Chinese Journal of Radiological Medicine and Protection,2025,45(11):1122-1129 |
| Short-term changes in energy metabolism of breast cancer cells under ultra-high dose rate irradiation |
| Received:July 08, 2025 |
| DOI：10.3760/cma.j.cn112271-20250708-00236 |
| KeyWords:Ultra-high dose rate irradiation Breast cancer Energy metabolism Mitochondria Glycolysis |
| FundProject:国家自然科学基金合作创新研究团队项目(W2541004);国家重点研发计划项目(2019YFF01014400);国家自然科学基金(12375334,11921006);北京大学第三医院临床重点项目(BYSYZD2024036) |
| Author Name | Affiliation | E-mail | | Luo Yunbin | State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing 100871, China
Laboratory of Femtosecond Laser and FLASH Radiotherapy, Peking University Third Hospital, Beijing 100191, China | | | Zhang Jiaying | Laboratory of Femtosecond Laser and FLASH Radiotherapy, Peking University Third Hospital, Beijing 100191, China
Beijing Key Laboratory for Interdisciplinary Research in Gastrointestinal Oncology, Department of Radiation Oncology, Peking University Third Hospital, Beijing 100191, China | | | Lyu Jianfeng | State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing 100871, China
Laboratory of Femtosecond Laser and FLASH Radiotherapy, Peking University Third Hospital, Beijing 100191, China | | | Wang Heming | State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing 100871, China
Laboratory of Femtosecond Laser and FLASH Radiotherapy, Peking University Third Hospital, Beijing 100191, China | | | Xue Lixiang | Laboratory of Femtosecond Laser and FLASH Radiotherapy, Peking University Third Hospital, Beijing 100191, China
Beijing Key Laboratory for Interdisciplinary Research in Gastrointestinal Oncology, Department of Radiation Oncology, Peking University Third Hospital, Beijing 100191, China | | | Wang Hao | Laboratory of Femtosecond Laser and FLASH Radiotherapy, Peking University Third Hospital, Beijing 100191, China
Beijing Key Laboratory for Interdisciplinary Research in Gastrointestinal Oncology, Department of Radiation Oncology, Peking University Third Hospital, Beijing 100191, China | | | Yang Gen | State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing 100871, China
Laboratory of Femtosecond Laser and FLASH Radiotherapy, Peking University Third Hospital, Beijing 100191, China | gen.yang@pku.edu.cn | | Yan Xueqing | State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing 100871, China
Laboratory of Femtosecond Laser and FLASH Radiotherapy, Peking University Third Hospital, Beijing 100191, China | |
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| Abstract:: |
| Objective To explore the time variations of the influence of the ultra-high dose rate irradiation (FLASH irradiation, FLASH-IR) and conventional dose rate irradiation (CONV-IR) of electron beams under different doses on the energy metabolism of triple-negative breast cancer cells MDA-MB-231. Methods The basal metabolism of the MDA-MB-231 cells and normal breast epithelial cells MCF-10A was compared using a Seahorse XF Pro Metabolic Analyzer. Based on an irradiation platform with a thermionic cathode electron accelerator (6 MeV), the MDA-MB-231 cells were exposed to FLASH-IR (106 Gy/s) and CONV-IR (0.1 Gy/s) at 2 and 14 Gy, respectively. Meanwhile, a sham irradiation group was established under identical culture conditions. The mitochondrial metabolism and glycolytic metabolism of the cells at 4, 24, and 48 h post-irradiation were analyzed. Results Compared to the MCF-10A cells, the MDA-MB-231 cells exhibited a greater reliance on glycolytic metabolism. Compared to those of the sham irradiation group, MDA-MB-231 cells in the 2 Gy CONV-IR group showed up-regulated ATP-linked respiration at 4, 24, and 48 h post-irradiation (t = 2.69-3.70, P < 0.05). Their glycolytic level and glycolytic capacity were up-regulated only at 4 h post-irradiation and were down-regulated at 48 h (t = 2.79, -4.44, P < 0.05). In contrast, there was no statistically significant difference in these indicators between the FLASH-IR and CONV-IR groups (P > 0.05). However, the proton leak of the MDA-MB-231 cells in the FLASH-IR group was relatively down-regulated at 4 h post-irradiation and was significantly up-regulated at 24 h and 48 h post-irradiation compared with the CONV-IR group (t = -2.45, 3.19, 6.51, P < 0.05). At 14 Gy, the MDA-MB-231 cells in the CONV-IR group showed progressively increased mitochondrial and glycolytic metabolism across all time points (t = 2.48-12.14, P < 0.05). Notably, compared with the CONV-IR group, the MDA-MB-231 cells in the FLASH-IR group exhibited more significantly up-regulated basal respiration, ATP-linked respiration, and non-mitochondrial oxygen consumption (t = 2.56-6.51, P < 0.05), as well as a higher glycolytic capacity at 24 h post-irradiation (t = 2.86, P < 0.05). Conclusions Low-dose (2 Gy) FLASH-IR induces relatively up-regulated proton leak in breast cancer cells MDA-MB-231 at 24 h post-irradiation. In contrast, under high-dose (14 Gy) FLASH-IR, the MDA-MB-231 cells show more pronounced mitochondrial metabolic stress and a higher demand for energy metabolism. |
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