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

X.-n. Li; H.-m. Bu; X.-h. Ma; Sh. Lu; Sh. Zhao; Y.-l. Cui; J. Sun

doi:10.1055/s-0042-112368

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2017; 125(02): 91-97
DOI: 10.1055/s-0042-112368

Article

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

Authors

X.-n. Li^*

²The Health Management Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
H.-m. Bu^*

¹Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
X.-h. Ma

¹Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Sh. Lu

³Outpatient Office, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Sh. Zhao

⁴Department of Pathology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Y.-l. Cui

¹Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
J. Sun

¹Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China

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

Full Text

References

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