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 culturedin 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 of TT (P>0.05); the calcitonin levels did not change signiifcantly 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.
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