Effects of new bombesin antagonists given singly or in combination with a somatostatin analog on nitrosamine-induced pancreatic cancers in hamsters

Karoly Szepeshazi, Andrew V Schally, Ren Zhi Cai, Gabor Halmos, Kate Groot

Research output: Contribution to journal › Article

6 Citations (Scopus)

Abstract

In three experiments, hamsters with N-nitroso-bis(2-oxopropyl)amine- induced pancreatic cancers were treated for two months with bombesin/GRP antagonists RC-3095 [D-Tpi6,Leu13'Ψ(CH2NH)Leu14-bombesin(6-14)], RC- 3910-II [D-Tpi6,Leu13'Ψ(CH2N)Tac14-bombesin(6-14)], RC-3940-II [Hca6,Leu13'Ψ(CH2N)Tac14-bombesin(6-14)], RC-3950-II [D- Phe6,Leu13'Ψ(CH2N)Tac14-bombesin(6-14)], somatostatin analog RC-160 (D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2), or the combination of RC-3095 with RC-160. All peptides inhibited pancreatic cancers to various degrees, reducing the number of tumorous animals, lowering the weight of tumorous pancreata by 40-55% and decreasing AgNOR numbers which are indicators of cell proliferation rate. Combination therapy with RC-3095 and RC-160 did not inhibit tumors better than single peptides. Among new bombesin/GRP antagonists, RC-3940-II had the strongest inhibitory effect. RC-3950-II and RC-3095 caused similar inhibition, but RC-3910-II was less effective. Tumor inhibitory activity of the bombesin/GRP antagonists was correlated with their binding affinities to bombesin receptors on tumor cells. RC-3940-II caused 50% inhibition of specific binding of [125I-Tyr4]bombesin to tumor cell membranes at 0.96 nM concentration, while the IC50 for RC- 3950-II was 5.27 nM and 12.94 nM for RC-3095. Our findings suggest that in addition to RC-3095, other bombesin/GRP antagonists such as RC-3950-II and especially RC-3940-II could be further developed for therapy of human pancreatic cancer.

Original languageEnglish
Pages (from-to)397-403
Number of pages7
JournalInternational Journal of Oncology
Volume9
Issue number3
StatePublished - Sep 1 1996
Externally publishedYes

Fingerprint

Bombesin
Nitrosamines
Somatostatin
Pancreatic Neoplasms
Cricetinae
Neoplasms
Bombesin Receptors
Peptides
Inhibitory Concentration 50
Amines
Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-bombesin (6-14)
Pancreas
Cell Proliferation
Cell Membrane
Weights and Measures
vapreotide
Hca(6)-Leu(13)-psi(CH2N)-Tac(14)-bombesin(6-14)

Keywords

  • AgNOR
  • antagonist
  • bombesin
  • bombesin
  • bombesin receptor
  • gastrin-releasing peptide
  • pancreatic cancer
  • somatostatin analog

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Effects of new bombesin antagonists given singly or in combination with a somatostatin analog on nitrosamine-induced pancreatic cancers in hamsters. / Szepeshazi, Karoly; Schally, Andrew V; Cai, Ren Zhi; Halmos, Gabor; Groot, Kate.

In: International Journal of Oncology, Vol. 9, No. 3, 01.09.1996, p. 397-403.

Research output: Contribution to journal › Article

Szepeshazi, K, Schally, AV, Cai, RZ, Halmos, G & Groot, K 1996, 'Effects of new bombesin antagonists given singly or in combination with a somatostatin analog on nitrosamine-induced pancreatic cancers in hamsters', International Journal of Oncology, vol. 9, no. 3, pp. 397-403.
Szepeshazi K, Schally AV, Cai RZ, Halmos G, Groot K. Effects of new bombesin antagonists given singly or in combination with a somatostatin analog on nitrosamine-induced pancreatic cancers in hamsters. International Journal of Oncology. 1996 Sep 1;9(3):397-403.
Szepeshazi, Karoly ; Schally, Andrew V ; Cai, Ren Zhi ; Halmos, Gabor ; Groot, Kate. / Effects of new bombesin antagonists given singly or in combination with a somatostatin analog on nitrosamine-induced pancreatic cancers in hamsters. In: International Journal of Oncology. 1996 ; Vol. 9, No. 3. pp. 397-403.
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abstract = "In three experiments, hamsters with N-nitroso-bis(2-oxopropyl)amine- induced pancreatic cancers were treated for two months with bombesin/GRP antagonists RC-3095 [D-Tpi6,Leu13'Ψ(CH2NH)Leu14-bombesin(6-14)], RC- 3910-II [D-Tpi6,Leu13'Ψ(CH2N)Tac14-bombesin(6-14)], RC-3940-II [Hca6,Leu13'Ψ(CH2N)Tac14-bombesin(6-14)], RC-3950-II [D- Phe6,Leu13'Ψ(CH2N)Tac14-bombesin(6-14)], somatostatin analog RC-160 (D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2), or the combination of RC-3095 with RC-160. All peptides inhibited pancreatic cancers to various degrees, reducing the number of tumorous animals, lowering the weight of tumorous pancreata by 40-55{\%} and decreasing AgNOR numbers which are indicators of cell proliferation rate. Combination therapy with RC-3095 and RC-160 did not inhibit tumors better than single peptides. Among new bombesin/GRP antagonists, RC-3940-II had the strongest inhibitory effect. RC-3950-II and RC-3095 caused similar inhibition, but RC-3910-II was less effective. Tumor inhibitory activity of the bombesin/GRP antagonists was correlated with their binding affinities to bombesin receptors on tumor cells. RC-3940-II caused 50{\%} inhibition of specific binding of [125I-Tyr4]bombesin to tumor cell membranes at 0.96 nM concentration, while the IC50 for RC- 3950-II was 5.27 nM and 12.94 nM for RC-3095. Our findings suggest that in addition to RC-3095, other bombesin/GRP antagonists such as RC-3950-II and especially RC-3940-II could be further developed for therapy of human pancreatic cancer.",
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T1 - Effects of new bombesin antagonists given singly or in combination with a somatostatin analog on nitrosamine-induced pancreatic cancers in hamsters

AU - Szepeshazi, Karoly

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AU - Halmos, Gabor

AU - Groot, Kate

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N2 - In three experiments, hamsters with N-nitroso-bis(2-oxopropyl)amine- induced pancreatic cancers were treated for two months with bombesin/GRP antagonists RC-3095 [D-Tpi6,Leu13'Ψ(CH2NH)Leu14-bombesin(6-14)], RC- 3910-II [D-Tpi6,Leu13'Ψ(CH2N)Tac14-bombesin(6-14)], RC-3940-II [Hca6,Leu13'Ψ(CH2N)Tac14-bombesin(6-14)], RC-3950-II [D- Phe6,Leu13'Ψ(CH2N)Tac14-bombesin(6-14)], somatostatin analog RC-160 (D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2), or the combination of RC-3095 with RC-160. All peptides inhibited pancreatic cancers to various degrees, reducing the number of tumorous animals, lowering the weight of tumorous pancreata by 40-55% and decreasing AgNOR numbers which are indicators of cell proliferation rate. Combination therapy with RC-3095 and RC-160 did not inhibit tumors better than single peptides. Among new bombesin/GRP antagonists, RC-3940-II had the strongest inhibitory effect. RC-3950-II and RC-3095 caused similar inhibition, but RC-3910-II was less effective. Tumor inhibitory activity of the bombesin/GRP antagonists was correlated with their binding affinities to bombesin receptors on tumor cells. RC-3940-II caused 50% inhibition of specific binding of [125I-Tyr4]bombesin to tumor cell membranes at 0.96 nM concentration, while the IC50 for RC- 3950-II was 5.27 nM and 12.94 nM for RC-3095. Our findings suggest that in addition to RC-3095, other bombesin/GRP antagonists such as RC-3950-II and especially RC-3940-II could be further developed for therapy of human pancreatic cancer.

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