| 商航,陆星宇,崔靓,等.FLASH照射与常规照射在乳腺癌的肿瘤控制和代谢途径改变的比较[J].中华放射医学与防护杂志,2025,45(11):1130-1137.Shang Hang,Lu Xingyu,Cui Liang,et al.Comparison of tumor control and metabolic pathway changes between FLASH irradiation and conventional irradiation in breast cancer[J].Chin J Radiol Med Prot,2025,45(11):1130-1137 |
| FLASH照射与常规照射在乳腺癌的肿瘤控制和代谢途径改变的比较 |
| Comparison of tumor control and metabolic pathway changes between FLASH irradiation and conventional irradiation in breast cancer |
| 投稿时间：2025-07-07 |
| DOI：10.3760/cma.j.cn112271-20250707-00230 |
| 中文关键词: FLASH照射 代谢组学 乳腺癌 肿瘤控制 |
| 英文关键词:FLASH irradiation Metabolomics Breast cancer Tumor control |
| 基金项目:国家自然科学基金(82272131) |
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| 中文摘要: |
| 目的 比较FLASH照射(FLASH-RT)与常规照射(CONV-RT)在小鼠乳腺癌模型中的抗肿瘤效应, 并分析各自影响的代谢物和代谢途径。方法 将进行乳腺癌荷瘤的雌性BALB/c小鼠用随机数表法随机分为3组:FLASH-RT(625 Gy/s, 23.64 Gy)、CONV-RT(0.54 Gy/s, 21.33 Gy)和假照射组(Sham-RT, 0 Gy/s), 单次照射。在2周内监测肿瘤体积, 随后对小鼠实施安乐死, 并收集肿瘤样本进行代谢组学分析。结果 FLASH照射与常规照射小鼠体质量变化差异无统计学意义(P>0.05), 与假照射组组相比, FLASH-RT(P<0.05)组和CONV-RT组(P<0.05)肿瘤体积变化差异均有统计学意义, 表明无论是FLASH-RT还是CONV-RT 均能有效抑制肿瘤生长。代谢组学分析表明, FLASH-RT显著下调了不饱和脂肪酸油酸(VIP= 1.867, FC=0.091)和脂类代谢物心磷脂(VIP=1.374, FC=0.419)的水平, 同时上调了饱和脂肪酸棕榈酸(VIP=1.592, FC=3.234)和磷脂酰胆碱(VIP=2.784, FC=4.116)的水平。差异代谢物主要富集在脂质代谢和氨基酸代谢通路中, 提示在肿瘤模型中存在能量代谢重编程及膜结构重塑的现象。通路富集分析显示, 甘油磷脂代谢途径被显著扰动(KEGG通路富集P<0.01), 相关代谢物磷脂酰胆碱含量显著升高, 达到CONV-RT组的4.12倍(VIP=2.784), 这种代谢紊乱可能反映癌细胞膜流动性改变或信号转导的异常。结论 FLASH-RT和CONV-RT均能有效抑制乳腺癌小鼠模型的肿瘤生长, 其中FLASH-RT表现出独特的代谢调节特性, 显示出FLASH-RT在乳腺癌治疗中的临床潜力。 |
| 英文摘要: |
| Objective To compare the antitumor effects of FLASH irradiation(FLASH-RT) and conventional irradiation (CONV-RT) in murine breast cancer models, alongside analyzing metabolites and metabolic pathways impacted by each treatment. Methods Female BALB/c mice bearing breast cancer tumors were randomly assigned to three groups: FLASH-RT(625 Gy/s, 23.64 Gy), CONV-RT(0.54 Gy/s, 21.33 Gy), and Sham-RT(0 Gy/s), with single irradiation. Tumor volumes were monitored over two weeks, after which mice were euthanized, and tumor samples were collected for metabolomic analysis. Results Statistical analysis indicated no significant difference in body weight changes between mice receiving FLASH and conventional irradiation (P>0.05). However, compared with the sham-irradiation group, both FLASH-RT (P<0.05) and CONV-RT (P<0.05) resulted in statistically significant differences in tumor volume changes, demonstrating effective tumor growth suppression by both radiotherapy regimens. Metabolomic analysis revealed that FLASH-RT significantly downregulated levels of the unsaturated fatty acid oleic acid (VIP=1.867, FC=0.091) and the lipid metabolite cardiolipin (VIP=1.373, FC=0.419), while upregulating the saturated fatty acid palmitic acid(VIP=1.592, FC=3.2343)and the lipid metabolite phosphatidylcholine(VIP=2.784, FC=4.116). Differential metabolites were predominantly enriched in lipid metabolism and amino acid metabolism pathways, suggesting energy metabolic reprogramming and membrane structural remodeling in the tumor model. Pathway enrichment analysis demonstrated significant perturbation in the glycerophospholipid metabolism pathway (KEGG pathway P<0.01), with its associated metabolite phosphatidylcholine (VIP=2.784) showing a marked increase, reaching 4.12-fold higher levels compared to the CONV-RT group..This metabolic dysregulation may reflect altered tumor cell membrane fluidity or aberrant signal transduction. Conclusions Both FLASH-RT and CONV-RT effectively inhibit tumor growth in murine breast cancer models, with FLASH-RT exhibiting distinct immunomodulatory metabolic characteristics, and the FLASH-RT shows the clinical potential in breast cancer therapy. |
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