Effects of CRF2R agonist on tumor growth and cachexia in mice implanted with lewis lung carcinoma cells
Effects of CRF2R agonist on tumor growth and cachexia in mice implanted with lewis lung carcinoma cells
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DOI：
10.1002/mus.20899
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发表时间：
2008-02-01
期刊：
影响因子：
3.4
通讯作者：
Busquets, Silvia
中科院分区：
文献类型：
--
作者：
Argiles, Josep M.;Figueras, Maite;Busquets, Silvia
先前的研究已经证明了促肾上腺皮质激素释放因子2受体（CRF 2 R）激动剂在维持骨骼肌质量中的作用。本研究的目的是评估CRF 2 R激动剂在小鼠恶病质模型中保存骨骼肌的作用。将快速生长的肿瘤（刘易斯肺癌）植入小鼠体内，导致明显的恶病质状态，其特征是严重的肌肉萎缩。我们发现，通过渗透微泵向荷瘤小鼠给予100 μ g/kg/天的CRF 2 R激动剂（PG-873637）对肌肉重量减轻产生有益作用。因此，在肿瘤生长的不同阶段，CRF 2 R激动剂部分逆转了肌肉损失（在肿瘤接种后第14天：胫骨后肌12%;腓肠肌9%;比目鱼肌48%）。此外，CRF 2 R激动剂显著降低了转移瘤的数量和质量（在肿瘤接种后第19天：分别为66%和61%）。这些数据表明CRF 2 R激动剂在癌症恶病质期间保护骨骼肌的潜在有益作用，并为开发治疗癌症相关肌肉萎缩的新治疗方法开辟了一条研究路线。
Previous studies have demonstrated an effect of corticotropin-releasing factor 2 receptor (CRF2R) agonists in the maintenance of skeletal muscle mass. The aim of this study was to evaluate the effects of a CRF2R agonist in preserving skeletal muscle in a mouse cachexia model. Implantation of a fast-growing tumor to mice (Lewis lung carcinoma) resulted in a clear cachectic state characterized by a profound muscle wasting. We found that administration of a CRF2R agonist (PG-873637) at 100 mu g/kg/day by means of osmotic minipumps to tumor-bearing mice resulted in beneficial effects on muscle weight loss. Thus, muscle loss was partially reversed by the CRF2R agonist at different stages of tumor growth (at day 14 after tumor inoculation: 12% in tibialis posterior; 9% in gastrocnemius; and 48% in soleus). Moreover, the CRF2R agonist significantly reduced both the number of metastases and their mass (at day 19 after tumor inoculation: 66% and 61%, respectively). These data suggest a potentially beneficial effect of the CRF2R agonist in preserving skeletal muscle during cancer cachexia and open a line of research for the development of new therapeutic approaches for the treatment of muscle wasting associated with cancer.