IR@PKUHSC  > 北京大学第三临床医学院
学科主题临床医学
Activation of glucagon-like peptide-1 receptor inhibits tumourigenicity and metastasis of human pancreatic cancer cells via PI3K/Akt pathway
Zhao, H.1; Wang, L.1; Wei, R.1; Xiu, D.2; Tao, M.2; Ke, J.1; Liu, Y.1; Yang, J.1; Hong, T.1
关键词diabetes glucagon-like peptide-1 metastasis pancreatic cancer tumourigenicity
刊名DIABETES OBESITY & METABOLISM
2014-09-01
DOI10.1111/dom.12291
16期:9页:850-860
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Endocrinology & Metabolism
资助者Chinese National 973 Program ; National Natural Sciences Foundation of China ; Specialized Research Fund for the Doctoral Program of Higher Education ; Chinese National 973 Program ; National Natural Sciences Foundation of China ; Specialized Research Fund for the Doctoral Program of Higher Education
研究领域[WOS]Endocrinology & Metabolism
关键词[WOS]DRUG-INDUCED PANCREATITIS ; GLP-1 ANALOG LIRAGLUTIDE ; EXOCRINE PANCREAS ; RISK-FACTORS ; NO EVIDENCE ; EXPRESSION ; ENDOCRINE ; GROWTH ; RATS ; INVASIVENESS
英文摘要

Aims: It has been reported that glucagon-like peptide-1 (GLP-1) agents are associated with an increased risk of pancreatic cancer in patients with type 2 diabetes. Reports have indicated that GLP-1 promotes pancreatic metaplasia and premalignant lesions. The aims of this study were to determine the effects of GLP-1-based therapy on pancreatic cancer cells.

Methods: Immunohistochemistry was used to investigate GLP-1 receptor (GLP-1R) expression in 30 human pancreatic cancer tissues. We also analysed associated clinicopathological data and each patient′s prognosis. Two human pancreatic cancer cell lines were used to evaluate the in vitro effects of the GLP-1R agonist liraglutide on cell growth, migration and invasion. Mouse xenograft models of human pancreatic cancer were established to evaluate the effects of liraglutide in vivo.

Results: Human pancreatic cancer tissues showed lower levels or a lack of GLP-1R expression when compared with levels in the tumour-adjacent pancreatic tissues. Negative GLP-1R expression occurred more frequently in advanced tumours with larger diameters and lymphatic metastasis, and was associated with a poor prognosis. GLP-1R activation with liraglutide inhibited tumourigenicity and metastasis of human pancreatic cancer cells in vitro and in vivo. Akt activation was dose-dependently inhibited by liraglutide, and the PI3K inhibitors, LY294002 and wortmannin, displayed similar suppressive effects to liraglutide in human pancreatic cancer cells.

Conclusions: GLP-1R activation has an antitumour effect on human pancreatic cancers via inhibition of the PI3K/Akt pathway. This finding suggests that GLP-1-based therapies may be beneficial, rather than harmful, in treating type 2 diabetic patients with pancreatic cancer.

语种英语
所属项目编号2012CB517502 ; 81070701 ; 81000315 ; 81270858 ; 20100001110083 ; 20120001120069 ; 20120001120063 ; 20120001120076
资助者Chinese National 973 Program ; National Natural Sciences Foundation of China ; Specialized Research Fund for the Doctoral Program of Higher Education ; Chinese National 973 Program ; National Natural Sciences Foundation of China ; Specialized Research Fund for the Doctoral Program of Higher Education
WOS记录号WOS:000340616400010
引用统计
被引频次:15[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/63894
专题北京大学第三临床医学院
作者单位1.Peking Univ, Hosp 3, Dept Endocrinol & Metab, Beijing 100191, Peoples R China
2.Peking Univ, Hosp 3, Dept Gen Surg, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Zhao, H.,Wang, L.,Wei, R.,et al. Activation of glucagon-like peptide-1 receptor inhibits tumourigenicity and metastasis of human pancreatic cancer cells via PI3K/Akt pathway[J]. DIABETES OBESITY & METABOLISM,2014,16(9):850-860.
APA Zhao, H..,Wang, L..,Wei, R..,Xiu, D..,Tao, M..,...&Hong, T..(2014).Activation of glucagon-like peptide-1 receptor inhibits tumourigenicity and metastasis of human pancreatic cancer cells via PI3K/Akt pathway.DIABETES OBESITY & METABOLISM,16(9),850-860.
MLA Zhao, H.,et al."Activation of glucagon-like peptide-1 receptor inhibits tumourigenicity and metastasis of human pancreatic cancer cells via PI3K/Akt pathway".DIABETES OBESITY & METABOLISM 16.9(2014):850-860.
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