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.

Abstract

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 microg/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.

• Authors: M Koppán, G Halmos, J M Arencibia, N Lamharzi, A V Schally
• Journal: Cancer (Cancer) Vol. 83 Issue 7 Pg. 1335-43 (Oct 01 1998) ISSN: 0008-543X [Print] United States
• PMID: 9762934 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Anticarcinogenic Agents
• Antigens, Neoplasm
• Antineoplastic Agents
• Membrane Glycoproteins
• Peptide Fragments
• RNA, Messenger
• TAA90K protein, human
• bombesin(6-14), Hca(6)-Leu(13)-psi(CH2N)-Tac(14)-
• bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-
• Gastrin-Releasing Peptide
• ErbB Receptors
• Bombesin

Topics

• Animals
• Anticarcinogenic Agents (pharmacology)
• Antigens, Neoplasm (analysis)
• Antineoplastic Agents (pharmacology)
• Blotting, Southern
• Bombesin (analogs & derivatives, antagonists & inhibitors, pharmacology)
• Carcinoma, Small Cell (genetics, metabolism, pathology)
• ErbB Receptors (analysis, genetics)
• Gastrin-Releasing Peptide (antagonists & inhibitors)
• Lung Neoplasms (genetics, metabolism, pathology)
• Male
• Membrane Glycoproteins (analysis)
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Peptide Fragments (pharmacology)
• Polymerase Chain Reaction
• RNA, Messenger (analysis)
• Transplantation, Heterologous
• Tumor Cells, Cultured