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
✍ Scribed by Miklós Koppán; Gábor Halmos; José M. Arencibia; Najib Lamharzi; Andrew V. Schally
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 134 KB
- Volume
- 83
- Category
- Article
- ISSN
- 0008-543X
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✦ Synopsis
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 g/animal/day.
RESULTS.
RC-3095 decreased tumor volume by approximately 50% (P Ͻ 0.05) and RC-3940-II by 70 -60% (P Ͻ 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 Ͻ 0.01) compared with controls, and EGF-R levels were reduced by 62.3% and 63.0%, respectively (both, P Ͻ 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 Ͻ 0.05) and 43% (P Ͻ 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.