Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
November 2013 Volume 30 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
November 2013 Volume 30 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Ghrelin inhibits ovarian epithelial carcinoma cell proliferation in vitro

  • Authors:
    • Yang Xu
    • Xiaoyan Pang
    • Mei Dong
    • Fang Wen
    • Yi Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Gynecology, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
  • Pages: 2063-2070
    |
    Published online on: August 23, 2013
       https://doi.org/10.3892/or.2013.2692
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The only orexigenic peptide, ghrelin, which is primarily produced by the gastrointestinal tract, has been implicated in malignant cell proliferation and invasion. Ghrelin is a natural ligand of the growth hormone secretagogue receptor 1a (GHSR1a). However, the role of ghrelin in ovarian epithelial carcinoma remains unknown since the expression of GHSR1a in ovary is not confirmed. The aim of the present study was to assess expression of ghrelin and its receptor in human ovarian epithelial carcinoma and to examine the effect of ghrelin on carcinoma cell proliferation. Frozen sections of ovarian samples and the human ovarian epithelial carcinoma cell line, HO-8910, were used to characterize the expression of ghrelin/GHSR1a axis and the effect of ghrelin on proli­feration. We found that ghrelin and GHSR1a are expressed in ovarian epithelial carcinoma in vivo and in vitro. Ghrelin inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest, and this inhibition may be abolished by the ghrelin receptor antagonist D-Lys-3-GH-releasing peptide-6 and ghrelin neutralizing antibody. Ghrelin enhances HO-8910 cell apoptosis and autophagy. The activation of mammalian target of rapamycin (mTOR) signaling pathway blocks the effects of ghrelin-induced autophagy and apoptosis, therefore reverses the inhibition of HO-8910 cell proliferation induced by ghrelin. In conclusion, the present study demonstrates that ghrelin inhibits the proliferation of human HO-8910 ovarian epithelial carcinoma cells by inducing apoptosis and autophagy via the mTOR signaling pathway. This study provides a novel regulatory signaling pathway of ghrelin-regulated ovarian epithelial carcinoma growth and may contribute to ovarian cancer prevention and therapy.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Billottet C, Janji B, Thiery JP and Jouanneau J: Rapid tumor development and potent vascularization are independent events in carcinoma producing FGF-1 or FGF-2. Oncogene. 21:8128–8139. 2002. View Article : Google Scholar : PubMed/NCBI

2 

Di Blasio AM, Cremonesi L, Viganó P, et al: Basic fibroblast growth factor and its receptor messenger ribonucleic acids are expressed in human ovarian epithelial neoplasms. Am J Obstet Gynecol. 169:1517–1523. 1993.PubMed/NCBI

3 

Chopin L, Walpole C, Seim I, et al: Ghrelin and cancer. Mol Cell Endocrinol. 340:65–69. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H and Kangawa K: Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 402:656–660. 1999. View Article : Google Scholar : PubMed/NCBI

5 

Kojima M and Kangawa K: Ghrelin: structure and function. Physiol Rev. 85:495–522. 2005. View Article : Google Scholar

6 

Smith RG, Leonard R, Bailey AR, et al: Growth hormone secretagogue receptor family members and ligands. Endocrine. 14:9–14. 2001. View Article : Google Scholar : PubMed/NCBI

7 

Majchrzak K, Szyszko K, Pawlowski KM, Motyl T and Król M: A role of ghrelin in cancerogenesis. Pol J Vet Sci. 15:189–197. 2012.PubMed/NCBI

8 

Zhang W, Lin TR, Hu Y, et al: Ghrelin stimulates neurogenesis in the dorsal motor nucleus of the vagus. J Physiol. 559:729–737. 2004. View Article : Google Scholar : PubMed/NCBI

9 

Kim SW, Her SJ, Park SJ, et al: Ghrelin stimulates proliferation and differentiation and inhibits apoptosis in osteoblastic MC3T3-E1 cells. Bone. 37:359–369. 2005. View Article : Google Scholar : PubMed/NCBI

10 

De Vriese C and Delporte C: Autocrine proliferative effect of ghrelin on leukemic HL-60 and THP-1 cells. J Endocrinol. 192:199–205. 2007.PubMed/NCBI

11 

Waseem T, Javaid-Ur-Rehman, Ahmad F, Azam M and Qureshi MA: Role of ghrelin axis in colorectal cancer: a novel association. Peptides. 29:1369–1376. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Ghè C, Cassoni P, Catapano F, et al: The antiproliferative effect of synthetic peptidyl GH secretagogues in human CALU-1 lung carcinoma cells. Endocrinology. 143:484–491. 2002.PubMed/NCBI

13 

Gnanapavan S, Kola B, Bustin SA, et al: The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab. 87:29882002. View Article : Google Scholar : PubMed/NCBI

14 

Gomez-Pinillos A and Ferrari AC: mTOR signaling pathway and mTOR inhibitors in cancer therapy. Hematol Oncol Clin North Am. 26:483–505. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Lynch CJ: Role of leucine in the regulation of mTOR by amino acids: revelations from structure-activity studies. J Nutr. 131:861S–865S. 2001.PubMed/NCBI

16 

Rosenfeldt MT and Ryan KM: The multiple roles of autophagy in cancer. Carcinogenesis. 32:955–963. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Mah LY and Ryan KM: Autophagy and cancer. Cold Spring Harb Perspect Biol. 4:a0088212012.PubMed/NCBI

18 

Gaytan F, Morales C, Barreiro ML, et al: Expression of growth hormone secretagogue receptor type 1a, the functional ghrelin receptor, in human ovarian surface epithelium, mullerian duct derivatives, and ovarian tumors. J Clin Endocrinol Metab. 90:1798–1804. 2005. View Article : Google Scholar

19 

Markowska A, Ziółkowska A, Jaszczyńska-Nowinka K, Madry R and Malendowicz LK: Elevated blood plasma concentrations of active ghrelin and obestatin in benign ovarian neoplasms and ovarian cancers. Eur J Gynaecol Oncol. 30:518–522. 2009.PubMed/NCBI

20 

Gutierrez JA, Solenberg PJ, Perkins DR, et al: Ghrelin octanoylation mediated by an orphan lipid transferase. Proc Natl Acad Sci USA. 105:6320–6325. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Yang J, Brown MS, Liang G, Grishin NV and Goldstein JL: Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone. Cell. 132:387–396. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Lim CT, Kola B, Grossman A and Korbonits M: The expression of ghrelin O-acyltransferase (GOAT) in human tissues. Endocr J. 58:707–710. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Zhang W, Chai B, Li JY, Wang H and Mulholland MW: Effect of des-acyl ghrelin on adiposity and glucose metabolism. Endocrinology. 149:4710–4716. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Hosoda H, Kojima M, Matsuo H and Kangawa K: Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue. Biochem Biophys Res Commun. 279:909–913. 2000. View Article : Google Scholar : PubMed/NCBI

25 

Inoki K, Corradetti MN and Guan KL: Dysregulation of the TSC-mTOR pathway in human disease. Nat Genet. 37:19–24. 2005. View Article : Google Scholar : PubMed/NCBI

26 

Yang Q and Guan KL: Expanding mTOR signaling. Cell Res. 17:666–681. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Laplante M and Sabatini DM: mTOR signaling in growth control and disease. Cell. 149:274–293. 2012. View Article : Google Scholar : PubMed/NCBI

28 

LoRusso PM: Mammalian target of rapamycin as a rational therapeutic target for breast cancer treatment. Oncology. 84:43–56. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Fuchs Y and Steller H: Programmed cell death in animal development and disease. Cell. 147:742–758. 2011. View Article : Google Scholar : PubMed/NCBI

30 

Bergmann A and Steller H: Apoptosis, stem cells, and tissue regeneration. Sci Signal. 3:re82010. View Article : Google Scholar : PubMed/NCBI

31 

Meijer AJ: Amino acids as regulators and components of nonproteinogenic pathways. J Nutr. 133:2057S–2062S. 2003.PubMed/NCBI

32 

Levine B and Klionsky DJ: Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell. 6:463–477. 2004. View Article : Google Scholar : PubMed/NCBI

33 

Crighton D, Wilkinson S, O’Prey J, et al: DRAM, a p53-induced modulator of autophagy, is critical for apoptosis. Cell. 126:121–134. 2006. View Article : Google Scholar : PubMed/NCBI

34 

Zhang H, Bosch-Marce M, Shimoda LA, et al: Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia. J Biol Chem. 283:10892–10903. 2008. View Article : Google Scholar : PubMed/NCBI

35 

Jung CH, Ro SH, Cao J, Otto NM and Kim DH: mTOR regulation of autophagy. FEBS Lett. 584:1287–1295. 2010. View Article : Google Scholar : PubMed/NCBI

36 

Chang YY, Juhász G, Goraksha-Hicks P, et al: Nutrient-dependent regulation of autophagy through the target of rapamycin pathway. Biochem Soc Trans. 37:232–236. 2009. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Xu Y, Pang X, Dong M, Wen F and Zhang Y: Ghrelin inhibits ovarian epithelial carcinoma cell proliferation in vitro. Oncol Rep 30: 2063-2070, 2013.
APA
Xu, Y., Pang, X., Dong, M., Wen, F., & Zhang, Y. (2013). Ghrelin inhibits ovarian epithelial carcinoma cell proliferation in vitro. Oncology Reports, 30, 2063-2070. https://doi.org/10.3892/or.2013.2692
MLA
Xu, Y., Pang, X., Dong, M., Wen, F., Zhang, Y."Ghrelin inhibits ovarian epithelial carcinoma cell proliferation in vitro". Oncology Reports 30.5 (2013): 2063-2070.
Chicago
Xu, Y., Pang, X., Dong, M., Wen, F., Zhang, Y."Ghrelin inhibits ovarian epithelial carcinoma cell proliferation in vitro". Oncology Reports 30, no. 5 (2013): 2063-2070. https://doi.org/10.3892/or.2013.2692
Copy and paste a formatted citation
x
Spandidos Publications style
Xu Y, Pang X, Dong M, Wen F and Zhang Y: Ghrelin inhibits ovarian epithelial carcinoma cell proliferation in vitro. Oncol Rep 30: 2063-2070, 2013.
APA
Xu, Y., Pang, X., Dong, M., Wen, F., & Zhang, Y. (2013). Ghrelin inhibits ovarian epithelial carcinoma cell proliferation in vitro. Oncology Reports, 30, 2063-2070. https://doi.org/10.3892/or.2013.2692
MLA
Xu, Y., Pang, X., Dong, M., Wen, F., Zhang, Y."Ghrelin inhibits ovarian epithelial carcinoma cell proliferation in vitro". Oncology Reports 30.5 (2013): 2063-2070.
Chicago
Xu, Y., Pang, X., Dong, M., Wen, F., Zhang, Y."Ghrelin inhibits ovarian epithelial carcinoma cell proliferation in vitro". Oncology Reports 30, no. 5 (2013): 2063-2070. https://doi.org/10.3892/or.2013.2692
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team