利拉鲁肽对人胰腺癌耐药细胞株增殖和凋亡的影响及机制研究  

Effect and Mechanism of Liraglutide on Proliferation and Apoptosis of Human Pancreatic Cancer Resistant Cell Lines

作　　者：赵荷珺[1] 段丽君[1] 任志鹏[2] ZHAO Hejun;DUAN Lijun;REN Zhipeng(Department of Endocrinology,Tianjin First Central Hospital,Tianjin 300192,China;Department of Orthopedics,Tianjin Hospital,Tianjin 300211,China)

机构地区：[1]天津市第一中心医院内分泌科,天津300192 [2]天津市天津医院骨科,天津300211

出　　处：《医学综述》2025年第1期118-124,共7页Medical Recapitulate

基　　金：国家自然科学基金(81602139);天津市卫生健康科技项目(TJWJ2024RC009);天津市科技计划项目多元投入基金项目青年项目(21JCQNJC01080)。

摘　　要：目的研究胰高糖素样肽1受体(GLP-1R)激动剂利拉鲁肽对人胰腺癌耐药细胞株PANC-1-GR增殖和凋亡的影响及机制。方法应用聚合酶链反应(PCR)和Western blot检测人胰腺癌细胞株PANC-1和人胰腺癌耐药细胞株PANC-1-GR中GLP-1R、蛋白激酶A(PKA)的表达,利用不同浓度(10、100、1000 nmol/L)利拉鲁肽处理PANC-1-GR细胞,PCR和Western blot检测GLP-1R/PKA信号通路的表达,细胞计数试剂盒8(CCK8)检测细胞增殖,流式细胞仪检测细胞凋亡,Western blot检测促凋亡蛋白的表达。分别加入GLP-1R拮抗剂Ex-9和PKA抑制剂H89,再次检测利拉鲁肽对细胞增殖和凋亡的影响。结果CCK8检测结果显示,与对照组相比,10、100及1000 nmol/L利拉鲁肽干预24 h和48 h后PANC-1-GR细胞增殖存活率降低(P<0.05)。Western blot结果显示,与对照组相比,10、100及1000 nmol/L利拉鲁肽干预24 h后PANC-1-GR细胞中促凋亡蛋白Bax和胱天蛋白酶3的表达升高(P<0.05);流式细胞仪检测结果显示,与对照组相比,10、100及1000 nmol/L利拉鲁肽干预24 h后PANC-1-GR细胞中凋亡细胞数量增加(P<0.05)。PCR和Western blot结果显示,与对照组相比,10、100及1000 nmol/L利拉鲁肽干预24 h后GLP-1R和PKA表达升高(P<0.05)。CCK8检测结果显示,与利拉鲁肽组相比,利拉鲁肽+Ex-9组和利拉鲁肽+H89组细胞增殖存活率升高(P<0.05)。流式细胞仪检测结果显示,与利拉鲁肽组相比,利拉鲁肽+Ex-9组和利拉鲁肽+H89组细胞凋亡率降低(P<0.05)。结论利拉鲁肽可抑制人胰腺癌耐药细胞增殖并促进其凋亡,其机制可能是通过激活GLP-1R/PKA信号通路实现的。Objective To investigate the effects and mechanism of glucagon-like peptide-1 receptor(GLP-1R)agonist liraglutide on the proliferation and apoptosis of the drug-resistant human pancreatic cancer cell line PANC-1-GR.Methods The expressions of GLP-1R and protein kinase A(PKA)in the human pancreatic cancer cell line PANC-1 and the drug-resistant cell line PANC-1-GR were detected by polymerase chain reaction(PCR)and Western blot.Then PANC-1-GR cells were treated with different concentrations of liraglutide(10,100,1000 nmol/L),the expression of GLP-1R/PKA signaling pathway detected by PCR and Western blot,cell proliferation determined by cell counting kit-8(CCK-8)analysis,cell apoptosis detected by flow cytometric analysis,and pro-apoptotic proteins detected by Western blot.GLP-1R antagonist Ex-9 and PKA inhibitor H89 were added with liraglutide to PANC-1-GR cells,and the effects of liraglutide on cell proliferation and apoptosis were tested again.Results The CCK8 test results showed that compared with the control group,the proliferative survival rate of PANC-1-GR cells decreased after intervention with 10,100,1000 nmol/L liraglutide for 24 h and 48 h(P<0.05).Western blot test results showed that compared with the control group,the expression of pro-apoptotic proteins Bax and caspase-3 in PANC-1-GR cells were increased after intervention with 10,100,1000 nmol/L liraglutide for 24 h(P<0.05).The results of flow cytometry analysis showed that compared with the control group,the number of apoptotic cells in PANC-1-GR cells increased after intervention with 10,100,1000 nmol/L liraglutide for 24 h(P<0.05).PCR and Western blot test results showed that compared with the control group,GLP-1R and PKA expressions were increased after intervention with 10,100,1000 nmol/L liraglutide for 24 h(P<0.05).The CCK8 test results showed that compared with the liraglutide group,the cell proliferation survival rate in liraglutide+Ex-9 group and liraglutide+H89 group was increased(P<0.05).The results of flow cytometry analysis showed that co

关 键 词：利拉鲁肽 胰高糖素样肽1受体 人胰腺癌耐药细胞 增殖 凋亡 

分 类 号：R587.1[医药卫生—内分泌]