PDF herunterladen
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
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 23. Dezember 2015
revised 31. Mai 2016

accepted 14. Juli 2016

Publikationsdatum:
22. Dezember 2016 (online)

Auch verfügbar auf
    Lizenzen und Reprints

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.


 

  • References

  • 1 Liu X, Hemminki K, Försti A et al. Cancer risk in patients with type 2 diabetes mellitus and their relatives. Int J Cancer 2015; 137: 903-910
    CrossrefPubMedSuche in Google Scholar
  • 2 Tabung F, Steck SE, Su LJ et al. Intake of grains and dietary fiber and prostate cancer aggressiveness by race. Prostate Cancer 2012; 2012: 323296
    PubMedSuche in Google Scholar
  • 3 Jemal A, Siegel R, Xu J et al. Cancer statistics, 2010. CA Cancer J Clin 2010; 60: 277-300
    CrossrefPubMedSuche in Google Scholar
  • 4 Clements A, Gao B, Yeap SHO et al. Metformin in prostate cancer: two for the price of one. Annals of Oncology 2011; 2556-2560
    PubMedSuche in Google Scholar
  • 5 Ussher JR, Drucker DJ. Cardiovascular biology of the incretin system. Endocr Rev 2012; 33: 187-215
    CrossrefPubMedSuche in Google Scholar
  • 6 Elashoff M, Matveyenko AV, Gier B et al. Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies. Gastroenterology 2011; 141: 150-156
    CrossrefPubMedSuche in Google Scholar
  • 7 Ahmad SR, Swann J. Exenatide and rare adverse events. N Engl J Med 2008; 358: 1970-1972
    PubMedSuche in Google Scholar
  • 8 Ligumsky H, Wolf I, Israeli S et al. The peptide-hormone glucagon-like peptide-1 activates cAMP and inhibits growth of breast cancer cells. Breast Cancer Res Treat 2012; 132: 449-461
    CrossrefPubMedSuche in Google Scholar
  • 9 Koehler JA, Kain T, Drucker DJ. Glucagon-like peptide-1 receptor activation inhibits growth and augments apoptosis in murine CT26 colon cancer cells. Endocrinology 2011; 152: 3362-3372
    CrossrefPubMedSuche in Google Scholar
  • 10 Gaddy DF, Riedel MJ, Pejawar-Gaddy S et al. In vivo expression of HGF/NK1 and GLP-1 From dsAAV vectors enhances pancreatic ß-cell proliferation and improves pathology in the db/db mouse model of diabetes. Diabetes 2010; 59: 3108-3116
    CrossrefPubMedSuche in Google Scholar
  • 11 Ravassa S, Zudaire A, Díez J. GLP-1 and cardioprotection: from bench to bedside. Cardiovasc Res 2012; 94: 316-323
    CrossrefPubMedSuche in Google Scholar
  • 12 Velmurugan K, Bouchard R, Mahaffey G et al. Neuroprotective actions of glucagon-like peptide-1 in differentiated human neuroprogenitor cells. J Neurochem 2012; 123: 919-931
    CrossrefPubMedSuche in Google Scholar
  • 13 Bjerre Knudsen L, Madsen LW, Andersen S et al. Glucagon-like Peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation. Endocrinology 2010; 151: 1473-1486
    CrossrefPubMedSuche in Google Scholar
  • 14 Nomiyama T, Kawanami T, Irie S et al. Exendin-4, a GLP-1 receptor agonist, attenuates prostate cancer growth. Diabetes 2014; 63: 3891-3905
    CrossrefPubMedSuche in Google Scholar
  • 15 Koehler JA, Drucker DJ. Activation of GLP-1 receptor signaling does not modify the growth or apoptosis of human pancreatic cancer cells. Diabetes 2006; 55: 1369-1379
    CrossrefPubMedSuche in Google Scholar
  • 16 Tsutsumi Y, Nomiyama T, Kawanami T et al. Combined Treatment with Exendin-4 and Metformin Attenuates Prostate Cancer Growth. PLoS One 2015; 10:
    PubMed
  • 17 Nomiyama T, Kawanami T, Irie S et al. Exendin-4, a GLP-1 receptor agonist, attenuates prostate cancer growth. Diabetes 2014; 63: 3891-3905
    CrossrefPubMedSuche in Google Scholar