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

doi:10.3109/02841869409121784

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 journal › Article › peer-review

55 Scopus citations

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 language	English (US)
Pages (from-to)	693-701
Number of pages	9
Journal	Acta Oncologica
Volume	33
Issue number	6
DOIs	https://doi.org/10.3109/02841869409121784
State	Published - 1994
Externally published	Yes

ASJC Scopus subject areas

Hematology
Oncology
Radiology Nuclear Medicine and imaging

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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, 1994, p. 693-701.

Research output: Contribution to journal › Article › peer-review

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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title = "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",

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.",

author = "Sinisa Radulovic and Schally, {Andrew V.} and Herta Reile and Gabor Halmos and Karoly Szepeshazi and Kate Groot and Slobodan Milovanovic and Glenn Miller and Tetsu Yano",

note = "Funding Information: We are grateful to Annamaria Zsigo and Harold Valerio for excellent experimental assistance. This work was supported by Public Health Service Grant CA 40077 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services; and by the Medical Research Service of the Dept. of Veterans Affairs (to A.V.S.). The gifts of materials used in radioimmunoassay from the National Hormone and Pituitary Program (NHPP) of National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) is greatly appreciated. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.",

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AU - Radulovic, Sinisa

AU - Schally, Andrew V.

AU - Reile, Herta

AU - Halmos, Gabor

AU - Szepeshazi, Karoly

AU - Groot, Kate

AU - Milovanovic, Slobodan

AU - Miller, Glenn

AU - Yano, Tetsu

N1 - Funding Information: We are grateful to Annamaria Zsigo and Harold Valerio for excellent experimental assistance. This work was supported by Public Health Service Grant CA 40077 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services; and by the Medical Research Service of the Dept. of Veterans Affairs (to A.V.S.). The gifts of materials used in radioimmunoassay from the National Hormone and Pituitary Program (NHPP) of National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) is greatly appreciated. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.

PY - 1994

Y1 - 1994

N2 - 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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