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Exp Clin Endocrinol Diabetes 2017; 125(02): 91-97
DOI: 10.1055/s-0042-112368
Article
© Georg Thieme Verlag KG Stuttgart · New York

Glucagon-like Peptide-1 Analogues Inhibit Proliferation and Increase Apoptosis of Human Prostate Cancer Cells in vitro

X.-n. Li   *
2   The Health Management Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
,
H.-m. Bu   *
1   Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
,
X.-h. Ma
1   Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
,
Sh. Lu
3   Outpatient Office, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
,
Sh. Zhao
4   Department of Pathology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
,
Y.-l. Cui
1   Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
,
J. Sun
1   Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
› Author Affiliations
Further Information

Publication History

received 23 December 2015
revised 31 May 2016

accepted 14 July 2016

Publication Date:
22 December 2016 (online)

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Abstract

Background: Research has shown that the incidence of prostate cancer is increased in patients with type 2 diabetes mellitus (T2DM) [1]. Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone that enhances glucose-dependent insulin secretion and suppresses glucagon release.

Method: Here, we examined the effect of exenatide and liraglutide, 2 types of GLP-1 analogues, on prostate cancer cells growth by CCK-8 assay, Hoechst33258 staining assay, and western blot analysis of apoptosis-related proteins Bax and Bcl-2. Also the kinase pathways maybe involved and the expression of GLP-1 receptor (GLP-1 R) in LNCap cells was detected.

Results: In our experiments, exenatide and liraglutide significantly inhibited the proliferation of the LNCap cell lines and induced the cell apoptosis. Exenatide (1–100 nmol/L) increased the ratio of Bax/Bcl-2 in a dose-dependent manner, whereas liraglutide increased Bax/Bcl-2 ratio only at concentrations of 10 nmol/L. And we found that GLP-1 analogues activate p38 but not ERK1/2 or AKT in LNCap cells. And classical GLP-1 receptor was detected in LNCap cells.

Conclusion: These data suggest that exenatide and liraglutide attenuate prostate cancer growth through regulating P38 pathway by binding with GLP-1R.

Key words

prostate cancer - glucagon-like peptide-1 - LNCap - apoptosis - proliferation

* Drs. LI and BU contributed equally to this article and share first authorship.


 

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