| 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].Chinese Journal of Radiological Medicine and Protection,2025,45(11):1130-1137 |
| Comparison of tumor control and metabolic pathway changes between FLASH irradiation and conventional irradiation in breast cancer |
| Received:July 07, 2025 |
| DOI：10.3760/cma.j.cn112271-20250707-00230 |
| KeyWords:FLASH irradiation Metabolomics Breast cancer Tumor control |
| FundProject:国家自然科学基金(82272131) |
| Author Name | Affiliation | E-mail | | Shang Hang | School of Biomedical Engineering, Southern Medical University, Guangzhou 510000, China | | | Lu Xingyu | School of Biomedical Engineering, Southern Medical University, Guangzhou 510000, China | | | Cui Liang | School of Biomedical Engineering, Southern Medical University, Guangzhou 510000, China | | | Zhou Linghong | School of Biomedical Engineering, Southern Medical University, Guangzhou 510000, China | smart@smu.edu.cn |
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| Abstract:: |
| 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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