| 罗筠彬,张嘉瑛,吕建锋,等.超高剂量率照射下乳腺癌细胞的短期能量代谢变化[J].中华放射医学与防护杂志,2025,45(11):1122-1129.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].Chin J Radiol Med Prot,2025,45(11):1122-1129 |
| 超高剂量率照射下乳腺癌细胞的短期能量代谢变化 |
| Short-term changes in energy metabolism of breast cancer cells under ultra-high dose rate irradiation |
| 投稿时间：2025-07-08 |
| DOI：10.3760/cma.j.cn112271-20250708-00236 |
| 中文关键词: 超高剂量率照射 乳腺癌 能量代谢 线粒体 糖酵解 |
| 英文关键词:Ultra-high dose rate irradiation Breast cancer Energy metabolism Mitochondria Glycolysis |
| 基金项目: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) |
| 作者 | 单位 | E-mail | | 罗筠彬 | 北京大学物理学院 核物理与核技术全国重点实验室, 北京 100871
北京大学第三医院飞秒激光与FLASH放疗实验室, 北京 100191 | | | 张嘉瑛 | 北京大学第三医院飞秒激光与FLASH放疗实验室, 北京 100191
北京大学第三医院肿瘤中心 胃肠肿瘤医-X协同创新北京市重点实验室, 北京 100191 | | | 吕建锋 | 北京大学物理学院 核物理与核技术全国重点实验室, 北京 100871
北京大学第三医院飞秒激光与FLASH放疗实验室, 北京 100191 | | | 王鹤茗 | 北京大学物理学院 核物理与核技术全国重点实验室, 北京 100871
北京大学第三医院飞秒激光与FLASH放疗实验室, 北京 100191 | | | 薛丽香 | 北京大学第三医院飞秒激光与FLASH放疗实验室, 北京 100191
北京大学第三医院肿瘤中心 胃肠肿瘤医-X协同创新北京市重点实验室, 北京 100191 | | | 王皓 | 北京大学第三医院飞秒激光与FLASH放疗实验室, 北京 100191
北京大学第三医院肿瘤中心 胃肠肿瘤医-X协同创新北京市重点实验室, 北京 100191 | | | 杨根 | 北京大学物理学院 核物理与核技术全国重点实验室, 北京 100871
北京大学第三医院飞秒激光与FLASH放疗实验室, 北京 100191 | gen.yang@pku.edu.cn | | 颜学庆 | 北京大学物理学院 核物理与核技术全国重点实验室, 北京 100871
北京大学第三医院飞秒激光与FLASH放疗实验室, 北京 100191 | |
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| 中文摘要: |
| 目的 探究不同剂量下电子线超高剂量率照射(FLASH-IR)和常规剂量率照射(CONV-IR)对三阴性乳腺癌细胞(MDA-MB-231)能量代谢影响随时间的变化。方法 使用Seahorse XF Pro细胞代谢分析仪对比了MDA-MB-231细胞和MCF-10A细胞的基础代谢差异。基于热阴极电子加速器(6 MeV)辐照平台, 将MDA-MB-231细胞分别以2 Gy与14 Gy的剂量暴露在FLASH-IR(106 Gy/s)和CONV-IR(0.1 Gy/s)下, 同时设置相同培养条件下的假照射组, 在照射后4、24、48 h分析线粒体代谢和糖酵解代谢。结果 乳腺癌细胞MDA-MB-231相较于正常乳腺细胞MCF-10A更倾向于糖酵解代谢。与假照射组相比, 2 Gy的CONV-IR在辐照后4、24及48 h均上调MDA-MB-231细胞ATP相关联呼吸水平(t=2.69~3.70, P＜0.05);而仅在4 h上调糖酵解水平和糖酵解潜力, 并在48 h后下调(t=2.79、-4.44, P＜0.05);相比之下, FLASH组相对CONV组在以上这些指标中的差异没有统计学意义(P＞0.05), 但在受照后4 h相对下调细胞质子渗漏水平, 并在24 h和48 h后显著上调(t=-2.45、3.19、6.51, P＜0.05)。14 Gy辐照条件下, CONV组在各时间点逐渐提升细胞线粒体代谢及糖酵解代谢水平(t=2.48~12.14, P＜0.05), 其中FLASH组相对CONV组在基础呼吸、ATP相关联呼吸和非线粒体氧消耗中均表现出更大程度的上调(t=2.56~6.51, P＜0.05), 并且在辐照后24 h表现出更高的糖酵解潜力(t=2.86, P＜0.05)。结论 低剂量(2 Gy)FLASH-IR会使乳腺癌细胞MDA-MB-231在24 h后相对上调质子渗漏水平, 高剂量(14 Gy)FLASH-IR会使乳腺癌细胞MDA-MB-231产生强烈的线粒体代谢应激, 表现出更强的能量代谢需求。 |
| 英文摘要: |
| 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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