Laboratory of Translational Oncology, Division of Imaging and Cancer, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.
Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.
J Cachexia Sarcopenia Muscle. 2021 Jun;12(3):796-810. doi: 10.1002/jcsm.12703. Epub 2021 May 6.
Skeletal muscle wasting and fatigue are commonly observed in cancer patients receiving chemotherapy and associated with reduced treatment outcome and quality of life. Nutritional support may mitigate these side effects, but potential interference with chemotherapy efficacy could be of concern. Here, we investigated the effects of an ω-3 polyunsaturated fatty acid (eicosapentaenoic acid and docosahexaenoic acid), leucine-enriched, high-protein (100% whey), additional vitamin D, and prebiotic fibres 'specific nutritional composition' (SNC) and chemotherapy on state-of-the-art tumour organoids and muscle cells and studied muscle function, physical activity, systemic inflammation, and chemotherapy efficacy in a mouse model of aggressive colorectal cancer (CRC).
Tumour-bearing mice received a diet with or without SNC. Chemotherapy treatment consisted of oxaliplatin and 5-fluorouracil. Tumour formation was monitored by calliper measurements. Physical activity was continuously monitored by infrared imaging. Ex vivo muscle performance was determined by myography, muscle fatty acid composition by gas chromatography, and plasma cytokine levels by Luminex xMAP technology. Patient-derived CRC organoids and C2C12 myotubes were used to determine whether SNC affects chemotherapy sensitivity in vitro.
Specific nutritional composition increased muscle contraction capacity of chemotherapy-treated tumour-bearing mice (P < 0.05) and enriched ω-3 fatty acid composition in muscle without affecting treatment efficacy (P < 0.0001). Mice receiving SNC maintained physical activity after chemotherapy and showed decreased systemic inflammation. Therapeutic response of CRC organoids was unaffected by SNC nutrients, while cell viability and protein synthesis of muscle cells significantly improved.
The results show that specialized nutritional support can be used to maintain muscle function and physical activity levels during chemotherapy without increasing tumour viability. Therefore, nutritional strategies have potential value in promoting cancer and chemotherapy tolerance.
接受化疗的癌症患者常出现骨骼肌消耗和疲劳，这与治疗结局和生活质量降低有关。营养支持可能会减轻这些副作用，但可能会影响化疗疗效。在此，我们研究了 ω-3 多不饱和脂肪酸（二十碳五烯酸和二十二碳六烯酸）、富含亮氨酸的高蛋白（100%乳清）、额外的维生素 D 和益生元纤维“特定营养成分”（SNC）与化疗对先进的肿瘤类器官和肌肉细胞的影响，并在侵袭性结直肠癌（CRC）小鼠模型中研究了肌肉功能、体力活动、全身炎症和化疗疗效。
荷瘤小鼠接受含或不含 SNC 的饮食。化疗治疗包括奥沙利铂和 5-氟尿嘧啶。通过卡尺测量监测肿瘤形成。通过红外成像连续监测体力活动。通过肌电图测定离体肌肉性能，通过气相色谱法测定肌肉脂肪酸组成，通过 Luminex xMAP 技术测定血浆细胞因子水平。使用患者来源的 CRC 类器官和 C2C12 肌管来确定 SNC 是否影响体外化疗敏感性。
SNC 增加了接受化疗的荷瘤小鼠的肌肉收缩能力（P<0.05），并在不影响治疗效果的情况下增加了肌肉中的 ω-3 脂肪酸组成（P<0.0001）。接受 SNC 的小鼠在化疗后保持体力活动，并显示出较低的全身炎症。SNC 营养素对 CRC 类器官的治疗反应没有影响，而肌肉细胞的细胞活力和蛋白质合成显著提高。
结果表明，专门的营养支持可用于在化疗期间维持肌肉功能和体力活动水平，而不会增加肿瘤活力。因此，营养策略在促进癌症和化疗耐受性方面具有潜在价值。
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