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Therapeutic Gene Delivery and Transfection in Human Pancreatic Cancer Cells using Epidermal Growth Factor Receptor-targeted Gelatin Nanoparticles
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Antagonists of growth hormone-releasing hormone (GH-RH) inhibit in vivo proliferation of experimental pancreatic

K Szepeshazi1, A V Schally, K Groot

  • 1Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, LA 70146, USA.

European Journal of Cancer (Oxford, England : 1990)
|March 31, 2000
PubMed

Insights

Growth hormone-releasing hormone (GH-RH) antagonists effectively inhibit pancreatic cancer growth by reducing insulin-like growth factor-II (IGF-II) production. This study demonstrates a novel therapeutic strategy targeting the IGF-II pathway in pancreatic tumors.

Area of Science:

  • Endocrinology and Cancer Biology
  • Molecular Oncology
  • Pharmacology

Background:

  • Insulin-like growth factors (IGF-I and IGF-II) are implicated in pancreatic cancer development.
  • Growth hormone-releasing hormone (GH-RH) antagonists modulate the GH-RH-GH-IGF-I axis and may directly impact tumor growth.
  • The specific role of IGF-II in GH-RH antagonist-mediated pancreatic cancer inhibition requires elucidation.

Purpose of the Study:

  • To investigate the efficacy of two GH-RH antagonists (MZ-4-71 and MZ-5-156) in experimental pancreatic cancer models.
  • To determine the involvement of IGF-I and IGF-II in the anti-tumor effects of GH-RH antagonists.

Main Methods:

  • Nitrosamine-induced pancreatic tumors in Syrian golden hamsters treated with GH-RH antagonist MZ-4-71.
  • Human pancreatic cancer SW-1990 xenografts in nude mice treated with GH-RH antagonists MZ-4-71 and MZ-5-156.
  • In vitro studies assessing cell proliferation, IGF-II mRNA expression, and IGF-II concentration in culture medium.

Main Results:

  • GH-RH antagonists significantly reduced tumor incidence, pancreatic weight, tumor volume, and tumor cell AgNOR counts in both models.
  • Therapy did not alter serum or tumor IGF-I levels, suggesting IGF-I is not involved in tumor inhibition.
  • Tumor IGF-II concentrations were significantly reduced (50-60%) by GH-RH antagonists; in vitro studies confirmed SW-1990 cells produce IGF-II, and the antagonist decreased its production and release.

Conclusions:

  • GH-RH antagonists exhibit potent inhibitory effects on experimental pancreatic cancer growth.
  • The anti-tumor activity of GH-RH antagonists in pancreatic cancer is likely mediated by a reduction in tumor IGF-II production and concentration.
  • These findings suggest GH-RH antagonists targeting the IGF-II pathway represent a promising therapeutic strategy for pancreatic cancer.

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