尽管癌症治疗在临床方面取得了进展，高死亡率仍然是一个巨大的挑战，需要大量的努力来寻找新的高效抗癌治疗方法。本研究旨在调查线粒体靶向抗氧化剂Mitoquinol (MitoQ)对Ehrlich腹水癌(EAC)小鼠模型中增殖的潜在影响。将携带肿瘤的小鼠分别给予两种剂量的MitoQ (0.3 mg & 0.5 mg/kg；每日i.p注射)或阿霉素 (2 mg/kg；每日i.p注射)治疗20天。EAC小鼠显示出严重的线粒体活性氧（mtROS）过度产生和线粒体膜电位（△Ψm）损伤。EAC小鼠表现出功能异常的线粒体自噬，伴有增强的厌氧酵解。此外，肿瘤细胞的增殖速率更高，同时刺激了细胞周期、侵袭和血管生成的标志物，并抑制了促凋亡蛋白，这些事件可能与NF-κB信号通路的激活相关。MitoQ的给药抑制了EAC小鼠中肿瘤细胞的存活和转移，从组织病理评估中可见肿瘤体积和重量减小，坏死区域数目增加。MitoQ通过抑制Cyclin D1 mRNA、MMP-1和CD34水平以及VEGF蛋白表达，抑制了肿瘤细胞的周期、侵袭和血管生成。这些观察结果与mtROS过度产生的消除与线粒体自噬蛋白PINK1/Parkin水平的增加，随后抑制NADH脱氢酶有关。值得注意的是，NF-κB信号通路得到了调节。本研究表明，通过维持mtROS和恢复线粒体自噬，MitoQ可对抗EAC小鼠肿瘤细胞的存活和进展，从而抑制NF-κB的活化。版权所有 © 2023 Elsevier Inc. 发表。

Despite the clinical advances in cancer treatment, the high mortality rate is still a great challenge, requiring much effort to find new and efficient cancer therapies.The present evidence investigated the potential antiproliferative impact of the mitochondrial-targeted antioxidant, Mitoquinol (MitoQ), on a mouse model of Ehrlich ascites carcinoma (EAC).Mice-bearing tumors were administered two doses of MitoQ (0.3 mg & 0.5 mg/kg; i.p daily) or doxorubicin (2 mg/kg; i.p daily) for 20 days.EAC mice revealed exacerbated mitochondrial reactive oxygen species (mtROS) and impaired mitochondrial membrane potential (△Ψm). Dysfunctional mitophagy was observed in EAC mice, along with boosting aerobic glycolysis. In addition, tumor cells exhibited higher proliferation rates, thereby stimulating cell cycle, invasion, and angiogenesis biomarkers together with suppressing proapoptotic proteins, events that might be correlated with activation of NF-κB signaling. The administration of MitoQ combated tumor cell survival and dissemination in EAC mice as evidenced by reducing tumor volumes and weights and increasing the number of necrotic areas in histopathological assessment. MitoQ also repressed tumor cell cycle, invasion, and angiogenesis via preventing cyclin D1 mRNA, MMP-1, and CD34 levels as well as VEGF protein expression. These observations were associated with the abrogation of mtROS overproduction and enhancement of the mitophagy proteins, PINK1/Parkin levels, followed by inhibition of NADH dehydrogenase. Notably, NF-κB signaling was modulated.This study suggests that MitoQ combated tumor cell survival and progression in EAC mice by maintaining mtROS and restoring mitophagy, thereby attenuation of NF-κB activation.Copyright © 2023. Published by Elsevier Inc.