Megestrol acetate: Its impact on muscle protein metabolism supports its use in cancer cachexia
Megestrol acetate: Its impact on muscle protein metabolism supports its use in cancer cachexia
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DOI：
10.1016/j.clnu.2010.06.003
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发表时间：
2010-12-01
影响因子：
6.3
通讯作者：
Argiles, Josep M.
中科院分区：
文献类型：
--
作者：
Busquets, Silvia;Serpe, Roberto;Argiles, Josep M.
背景和目标：恶病质是与癌症相关的多器官综合征，其特征在于体重减轻、肌肉和脂肪组织消耗和炎症，通常与厌食症相关。本研究的目的是检测醋酸甲地孕酮（MA）在恶病质荷瘤动物中的作用，分析肌肉蛋白水解和与生活质量相关的参数的变化。（100 mg/kg）在恶病质荷瘤大鼠中进行了试验结果：MA对荷瘤大鼠的给药导致肌肉萎缩过程的重要逆转，如个体肌肉重量所反映的。MA也降低了蛋白质降解率在孵育分离的骨骼肌。实时PCR分析显示，MA治疗导致肌肉中泛素，E2和atrogin-1 mRNA含量的减少，因此表明药物的主要抗蛋白水解作用可能是基于ATP-泛素依赖性蛋白水解系统的抑制。该药物还提高食欲，体重减轻，总体力活动和握力force.Conclusions：结果表明，治疗与甲地孕酮醋酸酯增加食欲，体重减轻，体力和肌肉力量在荷瘤大鼠表明MA是一个很好的候选人肌肉萎缩治疗。(C)2010年爱思唯尔有限公司和欧洲临床营养与代谢学会。All rights reserved.
Background & aims: Cachexia is a multiorganic syndrome associated with cancer, characterized by body weight loss, muscle and adipose tissue wasting and inflammation, being often associated with anorexia. The aim of the present investigation was to examine the effect of megestrol acetate (MA) in cachectic tumour-bearing animals analyzing changes in muscle proteolysis and in parameters related with quality of life.Methods: The effects of MA (100 mg/kg) were tested in cachectic tumour-bearing rats (Yoshida AH-130 ascites hepatoma).Results: Administration of MA to tumour-bearing rats resulted in an important reversal of the muscle wasting process, as reflected by individual muscle weights. MA also decreased the rate of protein degradation in incubated isolated skeletal muscles. Real-time PCR analysis revealed that MA treatment resulted in a decrease in ubiquitin, E2 and atrogin-1 mRNA content in muscles, therefore suggesting that the main anti-proteolytic action of the drug may be based on an inhibition of the ATP-ubiquitin-dependent proteolytic system. The drug also improves appetite, weight loss, total physical activity and grip force.Conclusions: The results indicate that treatment with megestrol acetate increases appetite, weight loss, physical performance and muscle force in tumour-bearing rats suggesting that MA is a good candidate for muscle wasting treatment. (C) 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.