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同基因B16F10黑色素瘤导致小鼠恶病质、骨骼肌力量受损和运动活动障碍。

Syngeneic B16F10 Melanoma Causes Cachexia and Impaired Skeletal Muscle Strength and Locomotor Activity in Mice.

作者信息

Voltarelli Fabrício A, Frajacomo Fernando T, Padilha Camila de Souza, Testa Mayra T J, Cella Paola S, Ribeiro Diogo F, de Oliveira Donizete X, Veronez Luciana C, Bisson Gabriela S, Moura Felipe A, Deminice Rafael

机构信息

Department of Physical Education, Faculty of Physical Education and Sport, State University of LondrinaLondrina, Brazil.

Department of Physical Education, Faculty of Physical Education, Federal University of Mato GrossoCuiabá, Brazil.

出版信息

Front Physiol. 2017 Sep 29;8:715. doi: 10.3389/fphys.2017.00715. eCollection 2017.

Abstract

Muscle wasting has been emerging as one of the principal components of cancer cachexia, leading to progressive impairment of work capacity. Despite early stages melanomas rarely promotes weight loss, the appearance of metastatic and/or solid tumor melanoma can leads to cachexia development. Here, we investigated the B16F10 tumor-induced cachexia and its contribution to muscle strength and locomotor-like activity impairment. C57BL/6 mice were subcutaneously injected with 5 × 10 B16F10 melanoma cells or PBS as a Sham negative control. Tumor growth was monitored during a period of 28 days. Compared to Sham mice, tumor group depicts a loss of skeletal muscle, as well as significantly reduced muscle grip strength and epididymal fat mass. This data are in agreement with mild to severe catabolic host response promoted by elevated serum tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and lactate dehydrogenase (LDH) activity. Tumor implantation has also compromised general locomotor activity and decreased exploratory behavior. Likewise, muscle loss, and elevated inflammatory interleukin were associated to muscle strength loss and locomotor activity impairment. In conclusion, our data demonstrated that subcutaneous B16F10 melanoma tumor-driven catabolic state in response to a pro-inflammatory environment that is associated with impaired skeletal muscle strength and decreased locomotor activity in tumor-bearing mice.

摘要

肌肉萎缩已逐渐成为癌症恶病质的主要组成部分之一,导致工作能力逐渐受损。尽管早期黑色素瘤很少导致体重减轻,但转移性和/或实体瘤黑色素瘤的出现会引发恶病质。在此,我们研究了B16F10肿瘤诱导的恶病质及其对肌肉力量和类似运动活动受损的影响。将C57BL/6小鼠皮下注射5×10个B16F10黑色素瘤细胞或作为假阴性对照的PBS。在28天内监测肿瘤生长情况。与假手术小鼠相比,肿瘤组出现骨骼肌丢失,以及肌肉握力和附睾脂肪量显著减少。这些数据与血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)升高和乳酸脱氢酶(LDH)活性所促进的轻度至重度分解代谢宿主反应一致。肿瘤植入还损害了一般运动活动并降低了探索行为。同样,肌肉丢失和炎症性白细胞介素升高与肌肉力量丧失和运动活动受损有关。总之,我们的数据表明,皮下B16F10黑色素瘤肿瘤在促炎环境下引发分解代谢状态,这与荷瘤小鼠骨骼肌力量受损和运动活动减少有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa8c/5626871/3e0a18d57062/fphys-08-00715-g0001.jpg

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