TY - JOUR
T1 - Bombesin/gastrin-releasing peptide antagonists RC-3095 and RC-3940-II inhibit tumor growth and decrease the levels and mRNA expression of epidermal growth factor receptors in H-69 small cell lung carcinoma
AU - Koppán, Miklós
AU - Halmos, Gábor
AU - Arencibia, José M.
AU - Lamharzi, Najib
AU - Schally, Andrew V.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1998/10/1
Y1 - 1998/10/1
N2 - BACKGROUND. Antagonists of bombesin/gastrin-releasing peptide (BN/GRP) have been developed to block the autocrine stimulatory effect of BN/GRP on tumors such as small cell lung carcinoma (SCLC). Although several studies have addressed the intracellular events that follow the formation of the receptor-ligand complex, the mechanism of action of BN/GRP antagonists remains unclear. METHODS. In this study the authors investigated the effect of synthetic BN/GRP antagonists RC-3095 and RC-3940-II on tumor growth and the expression of epidermal growth factor receptors (EGF-R) in H-69 SCLC. Athymic nude mice xenografted with H-69 SCLC were treated subcutaneously for 5 weeks with RC-3095 and RC-3940-II at the dose of 10 μg/animal/day. RESULTS. RC-3095 decreased tumor volume by approximately 50% (P < 0.05) and RC-3940-II by 70-60% (P < 0.01). Tumor burden also was significantly decreased in the groups treated with RC-3095 and RC-3940-II. Receptor analyses demonstrated high affinity binding sites for BN/GRP and EGF on the untreated H-69 SCLC tumors. After treatment with RC-3095 and RC-3940-II, the concentration of receptors for BN/GRP was decreased by 29.0% and 36.5%, respectively (both, P < 0.01) compared with controls, and EGF-R levels were reduced by 62.3% and 63.0%, respectively (both, P < 0.01). Reverse transcriptase-polymerase chain reaction and Southern blot analyses revealed that the levels of mRNA for EGF-R in tumors were lowered by 31% (P < 0.05) and 43% (P < 0.01), respectively, after treatment with RC-3095 and RC-3940- II. CONCLUSIONS. This study indicates that the inhibition of growth of H-69 SCLC by BN/GRP antagonists RC-3095 and RC-3940-II is accompanied by a marked decrease in the levels and mRNA expression of EGF-R.
AB - BACKGROUND. Antagonists of bombesin/gastrin-releasing peptide (BN/GRP) have been developed to block the autocrine stimulatory effect of BN/GRP on tumors such as small cell lung carcinoma (SCLC). Although several studies have addressed the intracellular events that follow the formation of the receptor-ligand complex, the mechanism of action of BN/GRP antagonists remains unclear. METHODS. In this study the authors investigated the effect of synthetic BN/GRP antagonists RC-3095 and RC-3940-II on tumor growth and the expression of epidermal growth factor receptors (EGF-R) in H-69 SCLC. Athymic nude mice xenografted with H-69 SCLC were treated subcutaneously for 5 weeks with RC-3095 and RC-3940-II at the dose of 10 μg/animal/day. RESULTS. RC-3095 decreased tumor volume by approximately 50% (P < 0.05) and RC-3940-II by 70-60% (P < 0.01). Tumor burden also was significantly decreased in the groups treated with RC-3095 and RC-3940-II. Receptor analyses demonstrated high affinity binding sites for BN/GRP and EGF on the untreated H-69 SCLC tumors. After treatment with RC-3095 and RC-3940-II, the concentration of receptors for BN/GRP was decreased by 29.0% and 36.5%, respectively (both, P < 0.01) compared with controls, and EGF-R levels were reduced by 62.3% and 63.0%, respectively (both, P < 0.01). Reverse transcriptase-polymerase chain reaction and Southern blot analyses revealed that the levels of mRNA for EGF-R in tumors were lowered by 31% (P < 0.05) and 43% (P < 0.01), respectively, after treatment with RC-3095 and RC-3940- II. CONCLUSIONS. This study indicates that the inhibition of growth of H-69 SCLC by BN/GRP antagonists RC-3095 and RC-3940-II is accompanied by a marked decrease in the levels and mRNA expression of EGF-R.
KW - Antagonists
KW - Bombesin
KW - Epidermal growth factor receptors
KW - Gastrin-releasing peptide
KW - Small cell lung carcinoma
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U2 - 10.1002/(SICI)1097-0142(19981001)83:7<1335::AID-CNCR10>3.0.CO;2-5
DO - 10.1002/(SICI)1097-0142(19981001)83:7<1335::AID-CNCR10>3.0.CO;2-5
M3 - Article
C2 - 9762934
AN - SCOPUS:0032189492
VL - 83
SP - 1335
EP - 1343
JO - Cancer
JF - Cancer
SN - 0008-543X
IS - 7
ER -