Abrahamsen Marie-Louise, Christensen Ida Bager, Laizāne Linda, Ahmed Haboon Ismail, Buch-Larsen Kristian, Marina Djordje, Andersson Michael, Schwarz Peter, Dela Flemming, Gillberg Linn
Xlab, Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark.
Laboratory of Sports and Nutrition Research, Riga Stradiņš University, Riga, Latvia.
Clin Exp Med. 2025 May 8;25(1):142. doi: 10.1007/s10238-025-01665-4.
Mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) has previously been shown to increase after chemo- and radiotherapy in early-stage breast cancer (BC) patients, but the persistence of the increase remains unknown. This study assessed whether changes in mitochondrial respiration and content in PBMCs from postmenopausal BC patients persist up to 1 year after treatment. Thirty-four early-stage BC patients were studied before, shortly after, and six- and twelve-months post-treatment along with 20 healthy controls. Mitochondrial respiration was measured using high-resolution respirometry of intact and permeabilized PBMCs. Mitochondrial content was estimated by quantifying mitochondrial DNA relative to nuclear DNA via qPCR. The mitochondrial respiratory capacity of intact and permeabilized PBMCs from BC patients significantly increased after adjuvant chemo- and radiotherapy (+ 33% and + 30% for the maximal capacity of the electron transport system, ETS), consistent with previous findings. Importantly, the respiratory capacity returned to pre-treatment levels six months after treatment completion in both intact and permeabilized cells (- 23% and - 26% for the ETS). Healthy controls exhibited similar mitochondrial respiration but had increased mitochondrial content (+ 20%) compared to BC patients before treatment. In summary, chemo- and radiotherapy transiently increased mitochondrial respiration in PBMCs, returning to baseline within six months after treatment completion. This temporary rise in oxygen demand may reflect immune system activation.
先前的研究表明，早期乳腺癌（BC）患者在化疗和放疗后，外周血单个核细胞（PBMC）中的线粒体呼吸作用会增强，但这种增强的持续性尚不清楚。本研究评估了绝经后BC患者PBMC中线粒体呼吸作用和含量的变化在治疗后1年内是否持续存在。研究了34例早期BC患者在治疗前、治疗后不久、治疗后6个月和12个月时的情况，并与20名健康对照者进行比较。使用完整和通透的PBMC的高分辨率呼吸测定法测量线粒体呼吸作用。通过qPCR定量线粒体DNA相对于核DNA的含量来估计线粒体含量。与先前的研究结果一致，辅助化疗和放疗后，BC患者完整和通透PBMC的线粒体呼吸能力显著增加（电子传递系统（ETS）的最大能力分别增加33%和30%）。重要的是，在治疗完成6个月后，完整和通透细胞中的呼吸能力均恢复到治疗前水平（ETS分别下降23%和26%）。健康对照者表现出相似的线粒体呼吸作用，但与治疗前的BC患者相比，线粒体含量增加（20%）。总之，化疗和放疗使PBMC中的线粒体呼吸作用短暂增强，在治疗完成后6个月内恢复到基线水平。这种氧气需求的暂时增加可能反映了免疫系统的激活。
