Skip to main content

Advertisement

SpringerLink
Log in

Limited short-term effects on human prostate cancer xenograft growth and epidermal growth factor receptor gene expression by the ghrelin receptor antagonist [D-Lys3]-GHRP-6

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Purpose

The ghrelin axis regulates many physiological functions (including appetite, metabolism, and energy balance) and plays a role in disease processes. As ghrelin stimulates prostate cancer proliferation, the ghrelin receptor antagonist [D-Lys3]-GHRP-6 is a potential treatment for castrate-resistant prostate cancer and for preventing the metabolic consequences of androgen-targeted therapies. We therefore explored the effect of [D-Lys3]-GHRP-6 on PC3 prostate cancer xenograft growth.

Methods

NOD/SCID mice with PC3 prostate cancer xenografts were administered 20 nmoles/mouse [D-Lys3]-GHRP-6 daily by intraperitoneal injection for 14 days and tumour volume and weight were measured. RNA sequencing of tumours was conducted to investigate expression changes following [D-Lys3]-GHRP-6 treatment. A second experiment, extending treatment time to 18 days and including a higher dose of [D-Lys3]-GHRP-6 (200 nmoles/mouse/day), was undertaken to ensure repeatability.

Results

We demonstrate here that daily intraperitoneal injection of 20 nmoles/mouse [D-Lys3]-GHRP-6 reduces PC3 prostate cancer xenograft tumour volume and weight in NOD/SCID mice at two weeks post treatment initiation. RNA-sequencing revealed reduced expression of epidermal growth factor receptor (EGFR) in these tumours. Further experiments demonstrated that the effects of [D-Lys3]-GHRP-6 are transitory and lost after 18 days of treatment.

Conclusions

We show that [D-Lys3]-GHRP-6 has transitory effects on prostate xenograft tumours in mice, which rapidly develop an apparent resistance to the antagonist. Although further studies on [D-Lys3]-GHRP-6 are warranted, we suggest that daily treatment with the antagonist is not a suitable treatment for advanced prostate cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. A.M. Wren, L.J. Seal, M.A. Cohen, A.E. Brynes, G.S. Frost, K.G. Murphy, W.S. Dhillo, M.A. Ghatei, S.R. Bloom, Ghrelin enhances appetite and increases food intake in humans. J. Clin. Endocrinol. Metab. 86(12), 5992 (2001)

    Article  CAS  PubMed  Google Scholar 

  2. M. Tschöp, R. Wawarta, R.L. Riepl, S. Friedrich, M. Bidlingmaier, R. Landgraf, C. Folwaczny, Post-prandial decrease of circulating human ghrelin levels. J. Endocrinol. Invest. 24(6), RC19–RC21 (2001)

    Article  PubMed  Google Scholar 

  3. M. Kojima, H. Hosoda, Y. Date, M. Nakazato, H. Matsuo, K. Kangawa, Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402(6762), 656–660 (1999). https://doi.org/10.1038/45230

    Article  CAS  Google Scholar 

  4. M. Tschöp, D.L. Smiley, M.L. Heiman, Ghrelin induces adiposity in rodents. Nature 407(6806), 908–913 (2000)

    Article  PubMed  Google Scholar 

  5. S.M. Abdel-Hakim, M.Y. Ibrahim, H.M. Ibrahim, M.M. Ibrahim, The effect of ghrelin antagonist (D-Lys3) GHRP-6 on ovariectomy-induced obesity in adult female albino rats. Endocr. Regul. 48(3), 126–134 (2014)

    Article  CAS  PubMed  Google Scholar 

  6. G. Xu, Z. Wang, Y. Li, Z. Li, H. Tang, J. Zhao, X. Xiang, L. Ding, L. Ma, F. Yuan, J. Fei, W. Wang, N. Wang, Y. Guan, C. Tang, M. Mulholland, W. Zhang, Ghrelin contributes to derangements of glucose metabolism induced by rapamycin in mice. Diabetologia 55(6), 1813–1823 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. J.N.T. Fung, P.L. Jeffery, J.D. Lee, I. Seim, D. Roche, A. Obermair, L.K. Chopin, C. Chen, Silencing of ghrelin receptor expression inhibits endometrial cancer cell growth in vitro and in vivo. Am. J. Physiol. Endocrinol. Metab. 305(2), E305–E313 (2013)

    Article  CAS  PubMed  Google Scholar 

  8. L.K. Chopin, I. Seim, C.M. Walpole, A.C. Herington, The ghrelin axis--does it have an appetite for cancer progression? Endocr. Rev. 33(6), 849–891 (2012)

    Article  CAS  PubMed  Google Scholar 

  9. P.L. Seim, L. Jeffery, C.M. de Amorim, J. Walpole, E.J. Fung, R. Whiteside, A.C. Lourie, L.K. Herington, Chopin, Ghrelin O-acyltransferase (GOAT) is expressed in prostate cancer tissues and cell lines and expression is differentially regulated in vitro by ghrelin. Reprod. Biol. Endocrinol. 11(1)70.1-70.9 (2013)

  10. P.L. Jeffery, A.C. Herington, L.K. Chopin, Expression and action of the growth hormone releasing peptide ghrelin and its receptor in prostate cancer cell lines. J. Endocrinol. 172(3), R7–R11 (2002)

    Article  CAS  PubMed  Google Scholar 

  11. I. Seim, A.A. Lubik, M.L. Lehman, N. Tomlinson, E.J. Whiteside, A.C. Herington, C.C. Nelson, L.K. Chopin, Cloning of a novel insulin-regulated ghrelin transcript in prostate cancer. J. Mol. Endocrinol. 50(2), 179–191 (2013)

    Article  CAS  PubMed  Google Scholar 

  12. D. Wacker, R.C. Stevens, B.L. Roth, How ligands illuminate GPCR molecular pharmacology. Cell 170(3), 414–427 (2017)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. J.L. Gomez, A.E. Ryabinin, The effects of ghrelin antagonists [D-Lys(3)]-GHRP-6 or JMV2959 on ethanol, water, and food intake in C57BL/6J mice. Alcohol Clin. Exp. Res 38(9), 2436–2444 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. A. Moulin, L. Demange, G. Bergé, D. Gagne, J. Ryan, D. Mousseaux, A. Heitz, D. Perrissoud, V. Locatelli, A. Torsello, J.-C. Galleyrand, J.-A. Fehrentz, J. Martinez, Toward potent ghrelin receptor ligands based ontrisubstituted 1,2,4-triazole structure. 2. synthesis and pharmacological in vitro and in vivo evaluations. J. Med. Chem. 50(23), 5790–5806 (2007)

    Article  CAS  PubMed  Google Scholar 

  15. S.H. Lockie, T. Dinan, A.J. Lawrence, S.J. Spencer, Z.B. Andrews, Diet-induced obesity causes ghrelin resistance in reward processing tasks. Psychoneuroendocrinology 62, 114–120 (2015)

    Article  CAS  PubMed  Google Scholar 

  16. D.I. Briggs, Z.B. Andrews, Metabolic status regulates ghrelin function on energy homeostasis. Neuroendocrinology 93(1), 48–57 (2011)

    Article  CAS  PubMed  Google Scholar 

  17. C.B. Steele, C.C. Thomas, S.J. Henley, G.M. Massetti, D.A. Galuska, T. Agurs-Collins, M. Puckett, L.C. Richardson, Richardson Vital signs: Trends in incidence of cancers associated with overweight and obesity — United States, 2005–2014 MMWR. Morbid Mortal Wkly Rep 66(39), 1052–1058 (2017)

    Article  Google Scholar 

  18. J. Ma, H. Li, E. Giovannucci, L. Mucci, W. Qiu, P.L. Nguyen, J.M. Gaziano, M. Pollak, M.J. Stampfer, Prediagnostic body-mass index, plasma C-peptide concentration, and prostate cancer-specific mortality in men with prostate cancer: A long-term survival analysis. Lancet Oncol. 9(11), 1039–1047 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Continuous update project report. Food, nutrition, physical activity, and the prevention of breast cancer. In: Research, World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project. (ed.). London: WCRF International, (2010)

  20. Continuous update project report. Food, nutrition, physical activity, and the prevention of endometrial cancer. In: Research, World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project. (ed.). London: WCRF International, (2013)

  21. Continuous update project report. Food, nutrition, physical activity, and the prevention of colorectal cancer. In: Research, World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project. (ed.). London: WCRF International, (2011)

  22. B. Holst, N.D. Holliday, A. Bach, C.E. Elling, H.M. Cox, T.W. Schwartz, Common structural basis for constitutive activity of the ghrelin receptor family. J. Biol. Chem. 279(51), 53806–53817 (2004)

    Article  CAS  PubMed  Google Scholar 

  23. D. Srisai, T.C. Yin, A.A. Lee, A.A.J. Rouault, N.A. Pearson, J.L. Grobe, J.A. Sebag, MRAP2 regulates ghrelin receptor signaling and hunger sensing. Nat. Commun. 8(1), 713 (2017)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. R.G. Smith, K. Cheng, W.R. Schoen, S.S. Pong, G. Hickey, T. Jacks, B. Butler, W.W.S. Chan, L.Y.P. Chaung, F. Judith, J. Taylor, M.J. Wyvratt, M.H. Fisher, A nonpeptidyl growth hormone secretagogue. Science 260(5114), 1640–1643 (1993)

    Article  CAS  PubMed  Google Scholar 

  25. K. Patel, V.D. Dixit, J.H. Lee, J.W. Kim, E.M. Schaffer, D. Nguyen, D.D. Taub, Identification of ghrelin receptor blocker, D-[Lys3] GHRP-6 as a CXCR4 receptor antagonist. Int J. Biol. Sci. 8(1), 108–117 (2012)

    Article  CAS  PubMed  Google Scholar 

  26. K. Patel, V.D. Dixit, J.H. Lee, J.W. Kim, E.M. Schaffer, D. Nguyen, D.D. Taub, The GHS-R blocker D-[Lys3] GHRP-6 serves as CCR5 chemokine receptor antagonist. Int J. Med. Sci. 9(1), 51–58 (2012)

    Article  CAS  PubMed  Google Scholar 

  27. E. Van der Meer, P.L.P. Van Loo, V. Baumans, Short-term effects of a disturbed light-dark cycle and environmental enrichment on aggression and stress-related parameters in male mice. Lab Anim. 38(4), 376–83 (2004)

    Article  CAS  PubMed  Google Scholar 

  28. H. Moon, J.E. Ruelcke, E. Choi, L.J. Sharpe, Z.D. Nassar, H. Bielefeldt-Ohmann, M.-O. Parat, A. Shah, M. Francois, K.L. Inder, A.J. Brown, P.J. Russell, R.G. Parton, M.M. Hill, Diet-induced hypercholesterolemia promotes androgen-independent prostate cancer metastasis via IQGAP1 and caveolin-1. Oncotarget 6(10), 7438–7453 (2015)

    Article  PubMed  PubMed Central  Google Scholar 

  29. T. Conway, J. Wazny, A. Bromage, M. Tymms, D. Sooraj, E.D. Williams, B. Beresford-Smith, Xenome--a tool for classifying reads from xenograft samples. Bioinformatics 28, i172–i178 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. D. Kim, G. Pertea, C. Trapnell, H. Pimentel, R. Kelley, S.L. Salzberg, TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 14(4), R36 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Y. Liao, G.K. Smyth, W. Shi, FeatureCounts: An efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30(7), 923–930 (2014)

    Article  CAS  Google Scholar 

  32. M.D. Robinson, A. Oshlack, A scaling normalization method for differential expression analysis of RNA-seq data. Genome Biol. 11(3), R25 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. M.D. Robinson, D.J. McCarthy, G.K. Smyth, EdgeR: A Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26(1), 139–140 (2010)

    Article  CAS  PubMed  Google Scholar 

  34. R. Gentleman, V. Carey, W. Huber, F. Hahne: Genefilter: methods for filtering genes from microarray experiments R package version In. R package version 3.3.3 (2016)

  35. M.E. Ritchie, B. Phipson, D. Wu, Y. Hu, C.W. Law, W. Shi, G.K. Smyth, limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43(7), e47 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. C.W. Law, Y. Chen, W. Shi, G.K. Smyth, Voom: Precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol. 15(2), R29 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. S. Durinck, P.T. Spellman, E. Birney, W. Huber, Mapping identifiers for the integration of genomic datasets with the R/Bioconductor package biomaRt. Nat. Protoc. 4(8), 1184–1191 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. D. Szklarczyk, J.H. Morris, H. Cook, M. Kuhn, S. Wyder, M. Simonovic, A. Santos, N.T. Doncheva, A. Roth, P. Bork, L.J. Jensen, C. von Mering, The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res. 45(D1), D362–D368 (2017)

    Article  CAS  PubMed  Google Scholar 

  39. D. Szklarczyk, A. Franceschini, S. Wyder, K. Forslund, D. Heller, J. Huerta-Cepas, M. Simonovic, A. Roth, A. Santos, K.P. Tsafou, M. Kuhn, P. Bork, L.J. Jensen, C. von Mering, STRINGv10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 43(Database issue), D447–D452 (2015)

    Article  CAS  PubMed  Google Scholar 

  40. A. Franceschini, D. Szklarczyk, S. Frankild, M. Kuhn, M. Simonovic, A. Roth, J. Lin, P. Minguez, P. Bork, C. von Mering, L.J. Jensen, STRINGv9.1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res. 41(Database issue), D808–D815 (2013)

    CAS  PubMed  Google Scholar 

  41. G. Csardi, T. Nepusz, The igraph software package for complex network research. Inter. Complex Syst. 1695(5), 1–9 (2006)

    Google Scholar 

  42. Z. Yang, R. Algesheimer, C.J. Tessone, A comparative analysis of community detection algorithms on artificial networks. Sci. Rep. 6, 30750 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. S.M. Hartig, Basic image analysis and manipulation in Image. J. In Frederick, M., Ausubel, F.M., Brent, R., Kingston, R.E., Moore, D.D., Seidman, J.G., Struhl, K. (eds.) Curr. Protoc. Mol. Biol. 102 pp14.15.1-14.15.12. John Wiley & Sons, Hoboken (2013)

  44. K.J. Livak, T.D. Schmittgen, Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25(4), 402–408 (2001)

    Article  CAS  PubMed  Google Scholar 

  45. G.S. Lien, C.H. Lin, Y.L. Yang, M.S. Wu, B.C. Chen, Ghrelin induces colon cancer cell proliferation through the GHS-R, Ras, PI3K, Akt, and mTOR signaling pathways. Eur. J. Pharmacol. 776, 124–131 (2016)

    Article  CAS  PubMed  Google Scholar 

  46. C. Tian, L. Zhang, D. Hu, J. Ji, Ghrelin induces gastric cancer cell proliferation, migration, and invasion through GHS-R/NF-kappaB signaling pathway. Mol. Cell Biochem. 382(1-2), 163–172 (2013)

    Article  CAS  PubMed  Google Scholar 

  47. R.X. Bai, W.P. Wang, P.W. Zhao, C.B. Li, Ghrelin attenuates the growth of HO-8910 ovarian cancer cells through the ERK pathway. Braz. J. Med. Biol. Res. 49(3) (2016). http://dx.doi.org/10.1590/1414-431X20155043

  48. F. Rossi, A. Castelli, M.J. Bianco, C. Bertone, M. Brama, V. Santiemma, Ghrelin induces proliferation in human aortic endothelial cells via ERK1/2 and PI3K/Akt activation. Peptides 29(11), 2046–2051 (2008)

    Article  CAS  PubMed  Google Scholar 

  49. H. Chung, E. Li, Y. Kim, S. Kim, S. Park, Multiple signaling pathways mediate ghrelin-induced proliferation of hippocampal neural stem cells. J. Endocrinol. 218(1), 49–59 (2013)

    Article  CAS  PubMed  Google Scholar 

  50. E. Baquedano, J.A. Chowen, J. Argente, L.M. Frago, Differential effects of GH and GH-releasing peptide-6 on astrocytes. J. Endocrinol. 218(3), 263–274 (2013)

    Article  CAS  PubMed  Google Scholar 

  51. N. Fukushima, R. Hanada, H. Teranishi, Y. Fukue, T. Tachibana, H. Ishikawa, S. Takeda, Y. Takeuchi, S. Fukumoto, K. Kangawa, K. Nagata, M. Kojima, Ghrelin directly regulates bone formation. J. Bone Miner. Res 20, 790–798 (2005)

    Article  CAS  PubMed  Google Scholar 

  52. D.H. Wang, Y.S. Hu, J.J. Du, Y.Y. Hu, W.D. Zhong, W.J. Qin, Ghrelin stimulates proliferation of human osteoblastic TE85 cells via NO/cGMP signaling pathway. Endocrine 35(1), 112–117 (2009)

    Article  CAS  PubMed  Google Scholar 

  53. D. Lin, Q. Wang, H. Ran, K. Liu, Y. Wang, J. Wang, Y. Liu, R. Chen, Y. Sun, R. Liu, F. Ding, Abnormal response to the anorexic effect of GHS-R inhibitors and exenatide in male Snord116 deletion mouse model for Prader-Willi syndrome. Endocrinology 155(7), 2355–2362 (2014)

    Article  CAS  PubMed  Google Scholar 

  54. K. Howick, B. Griffin, J. Cryan, H. Schellekens, From Belly to Brain: Targeting the ghrelin receptor in appetite and food intake regulation. Int J. Mol. Sci. 18(2), 273 (2017)

    Article  CAS  PubMed Central  Google Scholar 

  55. A. Asakawa, A. Inui, T. Kaga, G. Katsuura, M. Fujimiya, M.A. Fujino, M. Kasuga, Antagonism of ghrelin receptor reduces food intake and body weight gain in mice. Gut 52(7), 947–952 (2003)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. R. Mosa, L. Huang, H. Li, M. Grist, D. LeRoith, C. Chen, Long-term treatment with the ghrelin receptor antagonist [D-Lys3]-GHRP-6 does not improve glucose homeostasis in nonobese diabetic MKR mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 314(1), R71–r83 (2018)

    Article  CAS  PubMed  Google Scholar 

  57. J. Mendelsohn, J. Baselga, Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J. Clin. Oncol. 21(14), 2787–2799 (2003)

    Article  CAS  PubMed  Google Scholar 

  58. J.R. Grandis, A. Chakraborty, M.F. Melhem, Q. Zeng, D.J. Tweardy, Inhibition of epidermal growth factor receptor gene expression and function decreases proliferation of head and neck squamous carcinoma but not normal mucosal epithelial cells. Oncogene 15, 409 (1997)

    Article  CAS  Google Scholar 

  59. A.M. Traish, A. Morgentaler, Epidermal growth factor receptor expression escapes androgen regulation in prostate cancer: a potential molecular switch for tumour growth. Br. J. Cancer 101(12), 1949–1956 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Y. Gan, C. Shi, L. Inge, M. Hibner, J. Balducci, Y. Huang, Differential roles of ERK and Akt pathways in regulation of EGFR-mediated signaling and motility in prostate cancer cells. Oncogene 29, 4947 (2010)

    Article  CAS  PubMed  Google Scholar 

  61. Y. Huang, Y. Chang, X. Wang, J. Jiang, S.J. Frank, Growth hormone alters epidermal growth factor receptor binding affinity via activation of extracellular signal-regulated kinases in 3T3-F442A cells. Endocrinology 145(7), 3297–3306 (2004)

    Article  CAS  PubMed  Google Scholar 

  62. T. Waseem, M. Duxbury, S.W. Ashley, M.K. Robinson, Ghrelin promotes intestinal epithelial cell proliferation through PI3K/Akt pathway and EGFR trans-activation both converging to ERK 1/2 phosphorylation. Peptides 52(Supplement C), 113–121 (2014)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Health and Medical Research Council Australia (grant no. 1002255 and 1059021; to L.K.C., A.C.H., P.L.J., and I.S.), the Cancer Council Queensland (grant no. 1098565; to L.K.C., A.C.H., and I.S.), the Australian Research Council (grant no DP140100249; to L.K.C. and A.C.H.), a QUT Vice-Chancellor’s Senior Research Fellowship (to I.S.), the Movember Foundation and the Prostate Cancer Foundation of Australia through a Movember Revolutionary Team Award, the Australian Government Department of Health, and the Australian Prostate Cancer Research Center, Queensland (L.K.C., A.C.H., and C.C.N.).

Author information

Authors and Affiliations

  1. Ghrelin Research Group, Institute of Health and Biomedical Innovation, Translational Research Institute and School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia

    Michelle L. Maugham, Inge Seim, Patrick B. Thomas, Gabrielle J. Crisp, Esha T. Shah, Adrian C. Herington, Penny L. Jeffery & Lisa K. Chopin

  2. Australian Prostate Cancer Research Centre - Queensland, Princess Alexandra Hospital, Institute of Health and Biomedical Innovation, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, Australia

    Michelle L. Maugham, Inge Seim, Patrick B. Thomas, Gabrielle J. Crisp, Esha T. Shah, Adrian C. Herington, Colleen C. Nelson, Penny L. Jeffery & Lisa K. Chopin

  3. Comparative and Endocrine Biology Laboratory, Institute of Health and Biomedical Innovation, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, Australia

    Michelle L. Maugham, Inge Seim, Patrick B. Thomas, Gabrielle J. Crisp, Esha T. Shah, Penny L. Jeffery & Lisa K. Chopin

  4. Skeletal Biology and Forensic Anthropology Research Laboratory, Cancer Program, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, Australia

    Michelle L. Maugham & Laura S. Gregory

  5. Integrative Biology Laboratory, College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu, China

    Inge Seim

Authors
  1. Michelle L. Maugham
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Inge Seim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Patrick B. Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gabrielle J. Crisp
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Esha T. Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Adrian C. Herington
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Laura S. Gregory
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Colleen C. Nelson
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Penny L. Jeffery
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Lisa K. Chopin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lisa K. Chopin.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Ethical approval was granted from the University of Queensland and Queensland University of Technology Animal Ethics Committees (TRI/QUT/087/14/NHMRC).

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Maugham, M.L., Seim, I., Thomas, P.B. et al. Limited short-term effects on human prostate cancer xenograft growth and epidermal growth factor receptor gene expression by the ghrelin receptor antagonist [D-Lys3]-GHRP-6. Endocrine 64, 393–405 (2019). https://doi.org/10.1007/s12020-018-1796-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-018-1796-9

Keywords

Search

Navigation