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

Sinisa Radulovic, Andrew V Schally, Herta Reile, Gabor Halmos, Karoly Szepeshazi, Kate Groot, Slobodan Milovanovic, Glenn Miller, Tetsu Yano

Research output: Contribution to journalArticle

55 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)693-701
Number of pages9
JournalActa Oncologica
Volume33
Issue number6
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

Fingerprint

Gastrin-Releasing Peptide
Bombesin
Somatostatin
Nude Mice
Colonic Neoplasms
Growth
HT29 Cells
Neoplasms
Heterografts
Epidermal Growth Factor
Down-Regulation
Binding Sites
vapreotide
Cell Line
Injections
Membranes
Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-bombesin (6-14)

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Hematology

Cite this

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. / Radulovic, Sinisa; Schally, Andrew V; Reile, Herta; Halmos, Gabor; Szepeshazi, Karoly; Groot, Kate; Milovanovic, Slobodan; Miller, Glenn; Yano, Tetsu.

In: Acta Oncologica, Vol. 33, No. 6, 01.01.1994, p. 693-701.

Research output: Contribution to journalArticle

Radulovic, Sinisa ; Schally, Andrew V ; Reile, Herta ; Halmos, Gabor ; Szepeshazi, Karoly ; Groot, Kate ; Milovanovic, Slobodan ; Miller, Glenn ; Yano, Tetsu. / 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. In: Acta Oncologica. 1994 ; Vol. 33, No. 6. pp. 693-701.
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