Chemotherapy-induced muscle wasting: association with NF-κB and cancer cachexia.
Chemotherapy-induced muscle wasting: association with NF-κB and cancer cachexia.
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DOI：
10.4081/ejtm.2018.7590
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发表时间：
2018-04-24
影响因子：
2.2
通讯作者：
Guttridge DC
中科院分区：
文献类型：
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作者：
Damrauer JS;Stadler ME;Acharyya S;Baldwin AS;Couch ME;Guttridge DC
超过50%的所有癌症的复合特征是恶病质综合征的高发病率，恶病质综合征是一种复杂的代谢紊乱，其特征在于主要由于骨骼肌组织的总体消耗而导致的极度体重减轻。虽然对癌症恶病质原因的研究已经跨越了几十年，但对各种癌症治疗本身对恶病质的影响知之甚少。例如，化疗药物会引起恶心和厌食等副作用，但这些症状并不能完全解释癌症恶病质的变化。在这项研究中，我们研究了化疗化合物，特别是顺铂在结肠癌恶病质模型中的作用。我们发现，尽管顺铂能够如预期的那样减少肿瘤负荷，但小鼠的肌肉萎缩仍然存在。引人注目的是，顺铂单独被认为是调节肌肉萎缩，这是独立的通常牵连的泛素蛋白酶体系统。最后，我们发现顺铂能够诱导小鼠肌肉和肌管培养物中的NF-κB活性，这表明癌症治疗的另一个副作用是调节肌肉萎缩，这可能是通过激活NF-κB信号通路介导的。
A compounding feature of greater than 50% of all cancers is the high incidence of the cachexia syndrome, a complex metabolic disorder characterized by extreme weight loss due mainly to the gross depletion of skeletal muscle tissue. Although studies into the cause of cancer cachexia has spanned over multiple decades, little is known about the effects of various cancer treatments themselves on cachexia. For example, chemotherapy agents induce side effects such as nausea and anorexia, but these symptoms do not fully account for the changes seen with cancer cachexia. In this study we examine the effects of chemotherapeutic compounds, specifically, cisplatin in the colon-26 adenocarcinoma model of cancer cachexia. We find that although cisplatin is able to reduce tumor burden as expected, muscle wasting in mice nevertheless persists. Strikingly, cisplatin alone was seen to regulate muscle atrophy, which was independent of the commonly implicated ubiquitin proteasome system. Finally, we show that cisplatin is able to induce NF-κB activity in both mouse muscles and myotube cultures, suggesting that an additional side effect of cancer treatment is the regulation of muscle wasting that may be mediated through activation of the NF-κB signaling pathway.