【摘要】  目的  研究胰升血糖素样肽-1受体（GLP-1R）在人胰腺癌组织中的表达，并探讨GLP-1R激动剂利拉鲁肽对人胰腺癌细胞生长的影响。  方法  采用免疫组织化学法检测25例人胰腺癌组织中GLP-1R的表达情况，分析GLP-1R表达与肿瘤大小和生存时间的关系。采用利拉鲁肽干预两种人胰腺癌细胞系MIA PaCa-2和PANC-1后，采用RT-PCR和Western blot检测GLP-1R表达的变化，采用CCK-8增殖实验检测细胞的增殖，流式细胞仪检测细胞的凋亡。  结果  25例人胰腺癌组织中，GLP-1R表达阳性者13例（52%），与癌旁的胰腺组织比较，阳性表达水平降低。GLP-1R表达阴性的胰腺癌组织更常见于肿瘤大、生存时间短的胰腺癌患者。GLP-1R在MIA PaCa-2和PANC-1两种胰腺癌细胞中均可见表达，且利拉鲁肽可上调其GLP-1R表达水平。利拉鲁肽可抑制人胰腺癌细胞的增殖，促进人胰腺癌细胞的凋亡。  结论  GLP-1R表达可能有利于避免胰腺癌的进展，GLP-1R激动剂利拉鲁肽对人胰腺癌细胞具有抑制增殖和促进凋亡的作用。

【关键词】  胰升血糖素样肽-1；受体；胰腺癌；增殖；凋亡

The study on glucagon-like peptide-1 receptor activation and human pancreatic cancer  ZHAO He-jun, WANG Liang, TAO Ming, et al. Department of Endocrinology, Tianjin First Central Hospital, Tianjin 300192, China

【Abstract】  Objectives  To investigate glucagon-like peptide-1 receptor (GLP-1R) expression in human pancreatic cancer and to determine the influence of GLP-1R agonist Liraglutide on human pancreatic cancer cells.  Methods  GLP-1R expression was examined in 25 pancreatic cancer tissues by immunohistochemistry. The association of GLP-1R expression with tumour diameters and prognosis of pancreatic cancer patients was analyzed. Then the effects of GLP-1R agonist Liraglutide on GLP-1R expression were investigated in the human pancreatic cancer cell lines, MIA PaCa-2 and PANC-1, by RT-PCR and western blot analysis. CCK-8 assay was performed to investigate the effects of Liraglutide on pancreatic cancer cell proliferation, and cell apoptosis was assessed by flow cytometry using Annexin V and propidium iodide (PI) staining.  Results  GLP-1R staining was detected in 52% of the pancreatic tumours (13/25). Compared with tumour-adjacent pancreatic tissues, the levels of GLP-1R were lower or absent in the tumour tissues. Negative GLP-1R expression occurred more frequently in pancreatic cancer patients with a poorer overall survival rate and larger tumours. GLP-1R was detectable in both pancreatic cancer cells, and its expression was upregulated by 100 nmol/L liraglutide. Liraglutide inhibited the number of viable pancreatic cancer cells and induced apoptosis in a dose-dependent manner.  Conclusions  GLP-1R expression is beneficial in inhibiting pancreatic cancer progression, and GLP-1R agonist Liraglutide inhibits proliferation and induces apoptosis in human pancreatic cancer cell lines.