Kul Köprülü Tuğba, Aras Serhat, Erkal Çam Burçin, Kara Altan
Experimental Medicine Application and Research Center, University of Health Sciences, Uskudar, Istanbul, Turkey.
Department of Molecular Medicine, Hamidiye Instıtute of Health Sciences, University of Health Sciences, Uskudar, Istanbul, Turkey.
Breast Cancer. 2025 Jun 27. doi: 10.1007/s12282-025-01735-1.
The objective of this study was to investigate the acute radiobiological mechanisms underlying Flattening Filter (FF) and Flattening Filter Free (FFF) radiotherapy-induced inhibition of breast cancer (BCa) by detecting changes in gene expression levels. The study involved thirty-six adult nude mice models that were randomly divided into five groups: control (G1), breast cancer (BCa) (G2), FF-400 (G3), FFF-1120 (G4), and FFF-1820 (G5). The control group had no radiation or treatment, while the BCa group had a cancer model but no radiation. The BCa models were subjected to a single dose of 20 Gy of radiotherapy at varying dose rates: 400, 1120, and 1820 MU/min (G3, G4, and G5, respectively). Twenty days after implantation of the MCF-7 cancer cell line, nude mice were irradiated and sacrificed 48 h later for genetic analysis. A transcriptome library was created by extracting RNA from tissue samples. In the differentially expressed genes (DEG) analysis, a total of 1565 genes were found to be significantly altered in the G2 vs. G1 groups. When radiotherapy groups (G3, G4, and G5) were analyzed, 334 DEGs (231 down, 103 up) were identified in G3 vs G2 data, 167 DEGs (103 down, 64 up) in G4 vs G2 data, and 187 DEGs (116 down, 71 up) in G5 vs G2 data. Gene Ontology molecular function analysis revealed significant differences between groups G3 and G2, with an emphasis on protein binding, glutamate receptor activity, and interleukin-8 receptor activation. Similar features were observed when comparing groups G5 and G2. The analysis showed significant differences in the expression of the key ERAD pathway genes Ufd1 and Cav1 between the BCa and radiotherapy groups. It was concluded that the FFF beam significantly alters the processes underlying the ERAD pathway and glutamate receptor activation compared to the FF beam.
本研究的目的是通过检测基因表达水平的变化，探讨均整滤过器（FF）和无均整滤过器（FFF）放射治疗诱导乳腺癌（BCa）抑制的急性放射生物学机制。该研究涉及36只成年裸鼠模型，随机分为五组：对照组（G1）、乳腺癌组（BCa）（G2）、FF - 400组（G3）、FFF - 1120组（G4）和FFF - 1820组（G5）。对照组未接受辐射或治疗，而BCa组有癌症模型但未接受辐射。BCa模型以不同剂量率接受单次20 Gy放射治疗：400、1120和1820 MU/min（分别为G3、G4和G5组）。在植入MCF - 7癌细胞系20天后，对裸鼠进行照射，并在48小时后处死进行基因分析。通过从组织样本中提取RNA创建转录组文库。在差异表达基因（DEG）分析中，发现G2与G1组共有1565个基因发生显著改变。在分析放射治疗组（G3、G4和G5）时，G3与G2数据中鉴定出334个DEG（231个下调，103个上调），G4与G2数据中鉴定出167个DEG（103个下调，64个上调），G5与G2数据中鉴定出187个DEG（116个下调，71个上调）。基因本体分子功能分析显示G3和G2组之间存在显著差异，重点在于蛋白质结合、谷氨酸受体活性和白细胞介素 - 8受体激活。比较G5和G2组时也观察到类似特征。分析表明，BCa组和放射治疗组之间关键内质网相关蛋白降解（ERAD）途径基因Ufd1和Cav1的表达存在显著差异。得出的结论是，与FF束相比，FFF束显著改变了ERAD途径和谷氨酸受体激活的潜在过程。
