Inhibitory Effects of Antagonists of Bombesin/Gastrin Releasing Peptide (GRP) and Somatostatin Analog (RC-160) on Growth of HT-29 Human Colon Cancers in Nude Mice

Authors

  • Sinisa Radulovic Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, Louisiana, USA; Department of Medicine, Tulane University Medical School, New Orleans, Louisiana, USA
  • Andrew V. Schally Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, Louisiana, USA; Department of Medicine, Tulane University Medical School, New Orleans, Louisiana, USA
  • Herta Reile Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, Louisiana, USA; Department of Medicine, Tulane University Medical School, New Orleans, Louisiana, USA
  • Gabor Halmos Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, Louisiana, USA; Department of Medicine, Tulane University Medical School, New Orleans, Louisiana, USA
  • Karoly Szepeshazi Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, Louisiana, USA; Department of Medicine, Tulane University Medical School, New Orleans, Louisiana, USA
  • Kate Groot Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, Louisiana, USA; Department of Medicine, Tulane University Medical School, New Orleans, Louisiana, USA
  • Slobodan Milovanovic Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, Louisiana, USA; Department of Medicine, Tulane University Medical School, New Orleans, Louisiana, USA
  • Glenn Miller Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, Louisiana, USA; Department of Medicine, Tulane University Medical School, New Orleans, Louisiana, USA
  • Tetsu Yano Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, Louisiana, USA; Department of Medicine, Tulane University Medical School, New Orleans, Louisiana, USA

DOI:

https://doi.org/10.3109/02841869409121784

Abstract

Nude mice bearing xenografts of HT-29 human colon cancer cell line were treated for 4 weeks with somatostatin analog (RC-160), bombesin/gastrin releasing peptide (GRP) antagonists (RC-3095 and RC-3440). In three separate experiments somatostatin analog RC-160 (50 μg/day) released from microgranules significantly reduced tumor growth. Bombesin/GRP antagonists, RC-3095 and RC-3440 injected subcutaneously (s.c.) twice daily at a dose of 10 μg had the greatest and consistently significant inhibitory effect on tumor growth. RC-3095 given once daily s.c. at a dose of 20 μg was less effective. RC-3095 also inhibited metastatic tumor growth after intrasplenic injection of HT-29 cells in nude mice. Specific binding sites of somatostatin, bombesin and epidermal growth factor (EGF) were detected on intact HT-29 cells or on the membranes from HT-29 tumor xenografts. The inhibitory effects of bombesin antagonists on tumor growth were consistently linked with a significant down-regulation of EGF receptors. Bombesin/GRP antagonists and somatostatin analogs could be considered for the development of new hormonal therapies for colon cancer.

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Published

1994-01-01

How to Cite

Radulovic, S., Schally, A. V., Reile, H., Halmos, G., Szepeshazi, K., Groot, K., … Yano, T. (1994). Inhibitory Effects of Antagonists of Bombesin/Gastrin Releasing Peptide (GRP) and Somatostatin Analog (RC-160) on Growth of HT-29 Human Colon Cancers in Nude Mice. Acta Oncologica, 33(6), 693–701. https://doi.org/10.3109/02841869409121784