胰高糖素样肽-1受体激动剂对人甲状腺髓样癌细胞生长和能量代谢的影响  

Effect of glucagon-like peptide-1 receptor agonists on growth and energy metabolism in human medullary thyroid cancer cells

作　　者：王红[1] 张斯亮[1] 关海霞[1] 

机构地区：[1]中国医科大学附属第一医院内分泌科、内分泌研究所,辽宁省内分泌疾病重点实验室,辽宁沈阳110001

出　　处：《中国癌症杂志》2016年第6期487-491,共5页China Oncology

基　　金：辽宁省科学技术计划项目(2013225021)

摘　　要：背景与目的:胰高糖素样肽-1(glucagon like peptide-1,GLP-1)受体激动剂是一种新型降糖药。在研发过程中,发现其可增加啮齿类动物患甲状腺C细胞肿瘤的风险。因此,该药物对人类甲状腺的影响引人关注。本研究旨在探讨GLP-1受体激动剂对人甲状腺髓样癌(medullary thyroid cancer,MTC)细胞增殖、降钙素的分泌和能量代谢的影响。方法:体外培养人MTC细胞系(TT)。分别以0、1、10和100 nmol/L艾塞那肽和利拉鲁肽处理细胞24、48和72 h后,采用细胞计数试剂盒(cell counting kit-8,CCK-8)检测GLP-1受体激动剂艾塞那肽和利拉鲁肽处理后细胞增殖情况;采用降钙素试剂盒测定细胞培养上清液中降钙素水平的变化;采用Seahorse能量代谢分析仪检测细胞糖酵解及线粒体呼吸的变化。结果:实验组细胞增殖率与对照组相比,差异无统计学意义(P>0.05),降钙素的量与对照组相比,差异无统计学意义(P>0.05),不同浓度艾塞那肽和利拉鲁肽处理细胞24 h后,与对照组相比,实验组艾塞那肽和利拉鲁肽对MTC细胞能量代谢并无明显影响(P>0.05),随着艾塞那肽和利拉鲁肽处理时间延长,TT细胞糖酵解和线粒体呼吸并无明显改变(P>0.05)。结论:GLP-1受体激动剂对人MTC发生、发展无明显促进作用,未来仍需大规模临床数据进一步证实GLP-1受体激动剂的安全性。Background and purpose： This study aimed to investigate the effect of glucagon-like peptide-1 receptor agonists on proliferation, secretion of calcitonin and energy metabolism of medullary thyroid cancer （MTC） cell. Methods： The MTC cell line （TT） was cultured in vitro. After treatment with exenatide and liraglutide （0, 1, 10 and 100 nmol/L） for 24, 48 and 72 h, the proliferation of TT was analyzed by CCK-8 kit, the calcitonin was measured by calcitonin assay kits, and the energy metabolism of TT was measured by Seahorse XF instrument. Results： When compared with control group, neither exenatide nor liraglutide had effects on proliferation ofTT （P〉0.05）; the calcitonin levels did not change significantly after treatment with GLP-1 receptor agonists （P〉0.05）. Exenatide and liraglutide did not alter glycolysis and mitochondrial respiration in TT cells in a dose- and time-dependent manner. Conclusion： GLP-1 receptor agonists have no effect on the development of TT. Further collection of the safety data of exenatide and liraglutide on thyroid is still needed.

关 键 词：甲状腺髓样癌 艾塞那肽 利拉鲁肽 能量代谢 

分 类 号：R736.1[医药卫生—肿瘤]