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利拉鲁肽对人胰腺癌细胞增殖和凋亡的影响及可能机制
其他题名Effect and mechanism of liraglutide on proliferation and apoptosis of human pancreatic cancer cells
魏蕊; 杨进; 洪天配; 赵荷珺; 柯静; 侯文芳; 刘烨
关键词胰升糖素样肽 1 利拉鲁肽 人胰腺癌细胞 增殖 凋亡 Glucagon-like peptide-1 Liraglutide Human pancreatic cancer cells Proliferation Apoptosis
刊名中华内分泌代谢杂志
2015
DOI10.3760/cma.j.issn.1000-6699.2015.06.014
6页:530-534
收录类别中国科技核心期刊 ; 中文核心期刊 ; CSCD
文章类型Journal Article
摘要目的:观察胰升糖素样肽1(GLP-1)受体激动剂利拉鲁肽对人胰腺癌细胞增殖和凋亡的影响,并初步探讨可能的作用机制。方法体外培养的人胰腺癌细胞系 MIA PaCa-2应用10~1000 nmol/ L利拉鲁肽干预24 h 或100 nmol/ L 利拉鲁肽干预0~72 h。 CCK-8试剂盒检测细胞增殖,RT-PCR 和 Western印迹检测相关基因的 mRNA 和蛋白表达水平。结果 MIA PaCa-2细胞系表达 GLP-1受体。利拉鲁肽可剂量和时间依赖性抑制胰腺癌细胞增殖,上调促凋亡蛋白 Bax 的表达,抑制抗凋亡蛋白 Bcl2的表达。同时,利拉鲁肽还可剂量和时间依赖性抑制胰腺癌细胞的胰岛素受体( INSR)和胰岛素样生长因子1受体(IGF-1R)的表达,并且抑制下游信号分子 Erk1/2和 Akt 蛋白的磷酸化水平。结论利拉鲁肽可抑制人胰腺癌细胞增殖和促进其凋亡,其抑癌效应可能是通过下调 INSR 和 IGF-1R 的表达,继而抑制 MEK/ Erk1/2和 PI3k/ Akt 信号通路所介导的。 Objective To investigate the effects and mechanism of glucagon-like peptide-1 ( GLP-1 ) receptor agonist liraglutide on the proliferation and apoptosis of human pancreatic cancer cells. Methods The human pancreatic cancer cell line MIA PaCa-2 was incubated for 24 h with liraglutide at various concentrations (10-1 000 nmol/ L), or with 100 nmol/ L liraglutide for various durations (0-72 h). Cell proliferation was determined by Cell Counting Kit-8 (CCK-8) analysis. RT-PCR and Western blot were used to detect the mRNA and protein expression levels of related genes. Results GLP-1 receptor was expressed in the MIA PaCa-2 cells. Liraglutide suppressed cell proliferation, up-regulated the expression levels of pro-apoptotic protein Bax and down-regulated the expression levels of anti-apoptotic protein Bcl2 in human pancreatic cancer cells in a dose- and time-dependent manner. Meanwhile, liraglutide down-regulated the expression levels of insulin receptor (INSR) and insulin-like growth factor-1 receptor (IGF-1R), and the phosphorylation levels of their downstream signaling proteins Erk1 / 2 and Akt, in a dose- and time-dependent way. Conclusion Liraglutide inhibits proliferation and promotes apoptosis of human pancreatic cancer cells; the process may be mediated via suppressing the expression of INSR and IGF-1R and inhibiting activation of the downstream MEK/ Erk1 / 2 and PI3k/ Akt pathways.
语种中文
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文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/72786
Collection北京大学第三临床医学院_内分泌科
作者单位100191,北京大学第三医院内分泌科
Recommended Citation
GB/T 7714
魏蕊,杨进,洪天配,等. 利拉鲁肽对人胰腺癌细胞增殖和凋亡的影响及可能机制[J]. 中华内分泌代谢杂志,2015(6):530-534.
APA 魏蕊.,杨进.,洪天配.,赵荷珺.,柯静.,...&刘烨.(2015).利拉鲁肽对人胰腺癌细胞增殖和凋亡的影响及可能机制.中华内分泌代谢杂志(6),530-534.
MLA 魏蕊,et al."利拉鲁肽对人胰腺癌细胞增殖和凋亡的影响及可能机制".中华内分泌代谢杂志 .6(2015):530-534.
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