线粒体功能障碍是癌症恶病质（CC）的一个标志。肿瘤发病后不久，肌肉中的线粒体活性氧（ROS）就会升高。靶向线粒体 ROS 可能是预防 CC 的可行选择。本研究的目的是评估线粒体靶向抗氧化剂 SkQ1 在减轻两种生物性别 CC 方面的功效。雄性和雌性 Balb/c 小鼠双侧注射结肠 26 腺癌细胞 (C26) 细胞（总共 1x106 个细胞）或 PBS（等体积对照）。将 SkQ1 溶解在饮用水中（约 250 nmol/kg 体重/天），并在肿瘤诱导后 7 天开始给予小鼠，而对照组则饮用正常饮用水。在终点（肿瘤诱导后 25 天）评估背屈肌的体内肌肉收缩性、基于氧化氘的蛋白质合成、线粒体呼吸和线粒体 mRNA 含量、蛋白质周转和钙通道相关标记物。进行双向方差分析，然后在交互作用显着时 (p≤0.05) 进行 Tukey 事后检验。 SkQ1 减轻了 C26 雄性小鼠腓肠肌中癌症引起的萎缩，促进了蛋白质合成并减少了 Redd1 和 Atrogin 的诱导。在雌性小鼠中，无论肿瘤如何，SkQ1 都会减少荷瘤小鼠的肌肉质量，增加跖肌的分解代谢信号，并减少线粒体耗氧量。然而，在女性中，SkQ1 增强了背屈肌的肌肉收缩力，同时诱导 TA 中的 Ryr1、Serca1 和 Serca2a。总之，线粒体靶向抗氧化剂 SkQ1 可能会减轻 CC 引起的雄性肌肉损失，同时改善荷瘤雌性小鼠的肌肉收缩功能，表明这种线粒体疗法对 CC 的影响存在性别二态性。

Mitochondrial dysfunction is a hallmark of cancer cachexia (CC). Mitochondrial reactive oxygen species (ROS) are elevated in muscle shortly after tumor onset. Targeting mitochondrial ROS may be a viable option to prevent CC. The aim of this study was to evaluate the efficacy of a mitochondria-targeted antioxidant, SkQ1, to mitigate CC in both biological sexes. Male and female Balb/c mice were injected bilaterally with colon 26 adenocarcinoma (C26) cells (total 1x106 cells) or PBS (equal volume control). SkQ1 was dissolved in drinking water (~250 nmol/kg body weight/day) and administered to mice beginning seven days following tumor induction, while control groups consumed normal drinking water. In vivo muscle contractility of dorsiflexors, deuterium oxide-based protein synthesis, mitochondrial respiration and mRNA content of mitochondrial, protein turnover and calcium channel-related markers were assessed at endpoint (25 days following tumor induction). Two-way ANOVAs, followed by Tukey's post-hoc test when interactions were significant (p≤0.05), were performed. SkQ1 attenuated cancer-induced atrophy, promoted protein synthesis and abated Redd1 and Atrogin induction in gastrocnemius of C26 male mice. In female mice, SkQ1 decreased muscle mass and increased catabolic signaling in the plantaris of tumor-bearing mice, as well as reduced mitochondrial oxygen consumption, regardless of tumor. However, in females SkQ1 enhanced muscle contractility of the dorsiflexors with concurrent induction of Ryr1, Serca1 and Serca2a in TA. In conclusion, the mitochondria-targeted antioxidant SkQ1 may attenuate CC-induced muscle loss in males, while improving muscle contractile function in tumor-bearing female mice, suggesting sexual dimorphism in the effects of this mitochondrial therapy in CC.