No effect of unacylated ghrelin administration on subcutaneous PC3 xenograft growth or metabolic parameters in a Rag1-/- mouse model of metabolic dysfunction

PLoS One. 2018 Nov 20;13(11):e0198495. doi: 10.1371/journal.pone.0198495. eCollection 2018.

Abstract

Ghrelin is a peptide hormone which, when acylated, regulates appetite, energy balance and a range of other biological processes. Ghrelin predominately circulates in its unacylated form (unacylated ghrelin; UAG). UAG has a number of functions independent of acylated ghrelin, including modulation of metabolic parameters and cancer progression. UAG has also been postulated to antagonise some of the metabolic effects of acyl-ghrelin, including its effects on glucose and insulin regulation. In this study, Rag1-/- mice with high-fat diet-induced obesity and hyperinsulinaemia were subcutaneously implanted with PC3 prostate cancer xenografts to investigate the effect of UAG treatment on metabolic parameters and xenograft growth. Daily intraperitoneal injection of 100 μg/kg UAG had no effect on xenograft tumour growth in mice fed normal rodent chow or 23% high-fat diet. UAG significantly improved glucose tolerance in host Rag1-/- mice on a high-fat diet, but did not significantly improve other metabolic parameters. We propose that UAG is not likely to be an effective treatment for prostate cancer, with or without associated metabolic syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose
  • Cell Line, Tumor
  • Diet, High-Fat
  • Ghrelin / pharmacology*
  • Ghrelin / therapeutic use
  • Heterografts
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Hyperinsulinism / complications*
  • Hyperinsulinism / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Obesity / complications*
  • Obesity / metabolism
  • Prostatic Neoplasms / complications
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism

Substances

  • Blood Glucose
  • Ghrelin
  • Homeodomain Proteins
  • RAG-1 protein

Grants and funding

This work was supported by the National Health and Medical Research Council Australia (https://www.nhmrc.gov.au, grant nos 1002255 and 1059021; to L.K.C., A.C.H. and I.S.), the Cancer Council Queensland (https://cancerqld.org.au, grant no. 1098565; to L.K.C., A.C.H. and I.S.), the Australian Research Council (http://www.arc.gov.au/, 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, (http://www.prostate.org.au) the Australian Government Department of Health, and the Australian Prostate Cancer Research Centre-Queensland (L.K.C. and C.C.N.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.