Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
Department of Pharmacy - Drug Sciences, University of Bari, Bari, Italy.
Endocrine. 2017 Oct;58(1):106-114. doi: 10.1007/s12020-016-1184-2. Epub 2016 Nov 28.
Oncologic patients subjected to chemotherapy frequently present aphagia, malnutrition, and cachexia. The purpose of this study was to investigate whether selected growth hormone secretagogues including hexarelin, JMV2894 and JMV2951 could antagonize body weight loss and wasting induced by cisplatin administration in rats. The three growth hormone secretagogues behaved as full agonists of the growth hormone secretagogues receptor both in terms of ability to stimulate calcium mobilization in Chinese hamster ovary cells and stimulation of growth hormone release in neonatal rats. Adult rats were (i) treated with vehicle throughout (controls), or (ii) treated with cisplatin (days 1-3) and a growth hormone secretagogues or vehicle, (days 1-12). Body weight and food consumption were measured daily. Although all growth hormone secretagogues caused initial transient acute increases in food intake, the total amount of food eaten by controls and growth hormone secretagogues treated groups over the 12 experimental days was not significantly different. All groups pre-treated with cisplatin lost up to 5-10 % body weight in the first 4 days; they subsequently gained weight at a rate comparable with controls. Interestingly, rats which received JMV2894 demonstrated a faster gain in body weight than any other growth hormone secretagogues treated group and at the end of the protocol reached a weight similar to that of controls. JMV2894 did not stimulate perirenal and epididymal fat accumulation but reduced MuRF mRNA levels in skeletal muscles. In conclusion, our findings demonstrate that JMV2894 antagonizes cisplatin induced weight loss in rats and may prove useful in antagonizing cachexia associated with cancer and chemotherapy in humans.
接受化疗的肿瘤患者常出现厌食、营养不良和恶病质。本研究旨在探讨选择性生长激素促分泌素（包括 hexarelin、JMV2894 和 JMV2951）是否能拮抗顺铂给药引起的大鼠体重减轻和消耗。这三种生长激素促分泌素在刺激中国仓鼠卵巢细胞钙动员和刺激新生大鼠生长激素释放方面均表现为生长激素促分泌素受体的完全激动剂。成年大鼠（i）全程给予载体（对照组），或（ii）给予顺铂（第 1-3 天）和生长激素促分泌素或载体（第 1-12 天）。每日测量体重和食物摄入量。尽管所有生长激素促分泌素最初都会引起急性短暂的食物摄入量增加，但对照组和生长激素促分泌素处理组在 12 天实验期间摄入的总食物量没有显著差异。所有预先用顺铂处理的组在最初的 4 天内体重下降了 5-10%；随后它们以与对照组相当的速度增加体重。有趣的是，接受 JMV2894 治疗的大鼠体重增加速度比任何其他生长激素促分泌素处理组都快，在方案结束时体重与对照组相似。JMV2894 没有刺激肾周和附睾脂肪积累，但减少了骨骼肌中 MuRF mRNA 水平。总之，我们的研究结果表明，JMV2894 拮抗顺铂诱导的大鼠体重减轻，可能对拮抗癌症和化疗相关的恶病质有用。
