Exercise Reduces the Resumption of Tumor Growth and Proteolytic Pathways in the Skeletal Muscle of Mice Following Chemotherapy.
Exercise Reduces the Resumption of Tumor Growth and Proteolytic Pathways in the Skeletal Muscle of Mice Following Chemotherapy.
复制标题
DOI：
10.3390/cancers12113466
复制
发表时间：
2020-11-20
期刊：
影响因子：
5.2
通讯作者：
Rosa Neto JC
中科院分区：
文献类型：
--
作者：
Alves de Lima E Jr;Teixeira AAS;Biondo LA;Diniz TA;Silveira LS;Coletti D;Busquets Rius S;Rosa Neto JC
多柔比星是一种化疗药物，导致肌肉萎缩。基于许多癌症变体与恶病质相关以及癌症患者通常用化疗剂治疗的证据，确定减轻肌肉萎缩的策略是重要的。在癌症治疗期间，肌肉损失是一种预后不良的情况，运动已成为在这种情况下使用的潜在策略。一旦持续的化疗方案并不总是可行的，我们的研究结果表明，耐力运动的连续性是一种潜在的策略，可以在化疗需要中断时采用，最大限度地减少肿瘤生长的恢复并避免肌肉损失。肌肉萎缩的发病机制在癌症恶病质中起着核心作用，化疗有助于这种情况。因此，本研究旨在评估耐力运动对阿霉素引起的时间依赖性肌萎缩的影响。为此，C57 BL/6小鼠皮下接种刘易斯肺癌细胞（LLC组）。在肿瘤建立后一周，这些动物中的一组开始单独的阿霉素化疗（LLC + DOX组）或与耐力运动组合的阿霉素化疗（LLC + DOX + EXER组）。一组动物在化疗周期后安乐死，而其余动物在最后一次给予阿霉素后一周安乐死。运动与化疗相结合的实践显示出有益的效果，如化疗中断后肿瘤生长率的降低和多柔比星毒性导致的过早死亡的改善。此外，进行运动的小鼠中的蛋白质降解水平在化疗后恢复到基础水平;相反，仅用多柔比星治疗的小鼠经历了腓肠肌中蛋白水解途径的mRNA表达水平的增加（Trim 63、Fbxo 32、肌生长抑制素、FoxO）。总的来说，我们的研究结果表明，耐力运动可以在化疗期间和化疗后用于减轻阿霉素促进的肌肉萎缩，避免肿瘤生长的恢复。
Doxorubicin is a chemotherapeutic agent that contributes to muscle wasting. Based on the evidence that many cancer variants are associated with cachexia and that cancer patients are usually treated with chemotherapeutic agents, it is important to determine strategies to mitigate muscle atrophy. Muscle loss is a poor prognosis during cancer treatment, and exercise has emerged as a potential strategy utilized in this context. Once an ongoing regimen of chemotherapeutic treatment is not always possible, our results demonstrated that continuity of endurance exercise is a potential strategy that can be adopted when chemotherapy needs to be interrupted, minimizing the resumption of tumor growth and avoiding muscle loss. The pathogenesis of muscle atrophy plays a central role in cancer cachexia, and chemotherapy contributes to this condition. Therefore, the present study aimed to evaluate the effects of endurance exercise on time-dependent muscle atrophy caused by doxorubicin. For this, C57 BL/6 mice were subcutaneously inoculated with Lewis lung carcinoma cells (LLC group). One week after the tumor establishment, a group of these animals initiated the doxorubicin chemotherapy alone (LLC + DOX group) or combined with endurance exercise (LLC + DOX + EXER group). One group of animals was euthanized after the chemotherapy cycle, whereas the remaining animals were euthanized one week after the last administration of doxorubicin. The practice of exercise combined with chemotherapy showed beneficial effects such as a decrease in tumor growth rate after chemotherapy interruption and amelioration of premature death due to doxorubicin toxicity. Moreover, the protein degradation levels in mice undergoing exercise returned to basal levels after chemotherapy; in contrast, the mice treated with doxorubicin alone experienced an increase in the mRNA expression levels of the proteolytic pathways in gastrocnemius muscle (Trim63, Fbxo32, Myostatin, FoxO). Collectively, our results suggest that endurance exercise could be utilized during and after chemotherapy for mitigating muscle atrophy promoted by doxorubicin and avoid the resumption of tumor growth.
登录
查看更多内容
影响因子：
4.1
作者：
Hittel DS;Axelson M;Sarna N;Shearer J;Huffman KM;Kraus WE
通讯作者：
Kraus WE
影响因子：
3.7
作者：
Ando K;Takahashi F;Kato M;Kaneko N;Doi T;Ohe Y;Koizumi F;Nishio K;Takahashi K
通讯作者：
Takahashi K
影响因子：
3.3
作者：
Kavazis, Andreas N.;Smuder, Ashley J.;Powers, Scott K.
通讯作者：
Powers, Scott K.
影响因子：
4
作者：
Barreto R;Mandili G;Witzmann FA;Novelli F;Zimmers TA;Bonetto A
通讯作者：
Bonetto A
影响因子：
5.5
作者：
Allen, David L.;Unterman, Terry G.
通讯作者：
Unterman, Terry G.