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 language | English |
|---|---|
| Pages (from-to) | 397-403 |
| Number of pages | 7 |
| Journal | International Journal of Oncology |
| Volume | 9 |
| Issue number | 3 |
| State | Published - Sep 1 1996 |
| Externally published | Yes |
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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
}
TY - JOUR
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
AU - Schally, Andrew V
AU - Cai, Ren Zhi
AU - Halmos, Gabor
AU - Groot, Kate
PY - 1996/9/1
Y1 - 1996/9/1
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.
AB - 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.
KW - AgNOR
KW - antagonist
KW - bombesin
KW - bombesin
KW - bombesin receptor
KW - gastrin-releasing peptide
KW - pancreatic cancer
KW - somatostatin analog
UR - http://www.scopus.com/inward/record.url?scp=0029831380&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029831380&partnerID=8YFLogxK
M3 - Article
VL - 9
SP - 397
EP - 403
JO - International Journal of Oncology
JF - International Journal of Oncology
SN - 1019-6439
IS - 3
ER -