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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。
Objective To study the expression of GLP-1 receptor (GLP-1R) in human pancreatic cancer and investigate the effect of GLP-1R agonist liraglutide on the growth of human pancreatic cancer cells. Methods Immunohistochemistry was used to detect the expression of GLP-1R in 25 human pancreatic cancer tissues. The relationship between GLP-1R expression and tumor size and survival time was analyzed. After the two human pancreatic cancer cell lines MIA PaCa-2 and PANC-1 were treated with liraglutide, the changes of GLP-1R expression were detected by RT-PCR and Western blot. The proliferation and flow of the cells were detected by CCK-8 proliferation assay Cytometry to detect cell apoptosis. Results Thirteen cases (52%) had positive GLP-1R expression in 25 cases of human pancreatic cancer. The positive expression of GLP-1R in pancreatic cancer tissues was lower than that in the adjacent tissues. Pancreatic cancer tissues with negative GLP-1R expression are more common in patients with large tumors and short survival time. GLP-1R was found in both MIA PaCa-2 and PANC-1 pancreatic cancer cells, and liraglutide could up-regulate the expression of GLP-1R. Liraglutide can inhibit the proliferation of human pancreatic cancer cells and promote the apoptosis of human pancreatic cancer cells. Conclusion The GLP-1R expression may be helpful to prevent the progression of pancreatic cancer. The GLP-1R agonist liraglutide can inhibit the proliferation and promote the apoptosis of human pancreatic cancer cells.