中华放射医学与防护杂志

张俊,张思倩,王巧娟,等.质子FLASH照射和常规照射对肾癌细胞周期和死亡的影响[J].中华放射医学与防护杂志,2025,45(11):1100-1106.Zhang Jun,Zhang Siqian,Wang Qiaojuan,et al.Effects of proton FLASH irradiation and conventional irradiation on the cell cycle and death of renal cancer cells[J].Chin J Radiol Med Prot,2025,45(11):1100-1106

质子FLASH照射和常规照射对肾癌细胞周期和死亡的影响

Effects of proton FLASH irradiation and conventional irradiation on the cell cycle and death of renal cancer cells

投稿时间：2025-07-01

DOI：10.3760/cma.j.cn112271-20250701-00217

中文关键词: FLASH照射常规照射细胞周期细胞凋亡细胞焦亡

英文关键词:FLASH radiation Conventional radiation Cell cycle Apoptosis Pyroptosis

基金项目:国家自然科学基金面上项目(12575369,12275192);中核集团青年英才项目;学科建设托举工程项目(XKTJ-XK202410)

作者	单位	E-mail
张俊	苏州大学附属第二医院病理科, 苏州 215004
张思倩	苏州大学附属第二医院病理科, 苏州 215004
王巧娟	中国原子能科学研究院, 北京 102413
隋丽	中国原子能科学研究院, 北京 102413
张永胜	苏州大学附属第二医院病理科, 苏州 215004
曹志飞	苏州大学附属第二医院病理科, 苏州 215004	hunancao@163.com

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中文摘要:

目的探究质子FLASH照射(FLASH-IR)和常规照射(CONV-IR)对肾癌细胞周期、细胞凋亡和细胞焦亡的影响。方法分别给予人肾癌细胞株769-P 8 Gy质子照射, FLASH-IR的剂量率为40 Gy/s, CONV-IR的剂量率为 0.4 Gy/s, 对照(Ctrl)组不照射。照射后24 h收集细胞, 采用流式细胞术检测细胞周期变化。采用实时荧光定量聚合酶链式反应(RT-qPCR)和蛋白免疫印迹实验, 检测肾癌细胞周期、凋亡和焦亡信号通路相关基因与蛋白表达情况。结果质子FLASH-IR使G₀/G₁期肾癌细胞比例增加[FLASH-IR组vs.Ctrl组 :( 67.01±0.44)% vs.(38.68±0.63)%, t = -63.99, P ＜0.05], 而CONV-IR使G₂/M期肾癌细胞比例增加[CONV-IR组vs.Ctrl组 :(56.65±1.52)% vs.(23.67±0.51)%, t = -29.17, P ＜0.05]。质子FLASH-IR和CONV-IR均导致肾癌细胞发生凋亡(t_FLASH = -16.24~-5.01, P ＜0.05;t_CONV=-20.08~6.11, P＜0.05)并且CONV-IR激活P53/P21通路(t= -16.86~-9.74, P ＜0.05)。质子FLASH-IR和CONV-IR同样诱导肾癌细胞发生焦亡(t_FLASH = -23.36~20.18, P ＜0.05;t_CONV=-41.62~13.95, P＜0.05), 且与CONV-IR相比, 质子FLASH-IR使肾癌细胞发生焦亡的程度更高(FLASH-IR组vs.CONV-IR:0.96±0.01 vs. 0.68±0.44, t = -10.46, P＜0.05)。结论质子FLASH照射和常规照射均会影响肾癌细胞周期变化, 促进细胞凋亡和焦亡, 但两者存在差异, 其机制有待进一步探索。质子FLASH照射在肾癌治疗中有潜在应用价值。

英文摘要:

Objective To explore the effects of proton FLASH irradiation (FLASH-IR) and conventional irradiation (CONV-IR) on the cell cycle, apoptosis, and pyroptosis of renal cancer cells. Methods Renal cancer cells (769-P) were irradiated with 8 Gy of protons at a dose rate of 40 Gy/s for FLASH-IR and 0.4 Gy/s for CONV-IR, Ctrl group was treated without irradiation. Cells were collected 24 h after irradiation. The changes in the cell cycle were measured using flow cytometry. The expression of genes and proteins related to the cell cycle, apoptosis, and pyroptosis signaling pathways in renal cancer cells was measured using quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot. Results Proton FLASH-IR increased the proportion of renal cancer cells in the G₀/G₁ phase [FLASH-IR group vs. Ctrl group, (67.01±0.44)% vs. (38.68±0.63)%, t = -63.99, P＜0.05], while CONV-IR increased the proportion of renal cancer cells in the G₂/M phase [CONV-IR group vs. Ctrl group, (56.65±1.52)% vs. (23.67±0.51)%, t = -29.17, P＜0.05]. Both proton FLASH-IR and CONV-IR caused apoptosis of renal cancer cells (t_FLASH= -16.24 to -5.01, P <0.05; t_CONV=-20.08 to 6.11, P< 0.05) and CONV-IR activated the P53/P21 pathway (t = -16.86 to -9.74, P < 0.05). Both proton FLASH-IR and CONV-IR induced pyroptosis of renal cancer cells (t_FLASH= -23.36 to 20.18, P <0.05; t_CONV=-41.62 to 13.95, P<0.05), and the former exhibited a greater effect (FLASH-IR group vs. CONV-IR group, 0.96±0.01 vs. 0.68±0.44, t = -10.46, P <0.05). Conclusions Both proton FLASH-IR and CONV-IR bring about changes in the cell cycle of renal cancer, promoting apoptosis and pyroptosis. However, there are differences between the two mechanisms that require further exploration. Proton FLASH-IR holds promise for the treatment of renal cancer.

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