Inhibition of growth of MDA-MB-468 estrogen-independent human breast carcinoma by bombesin/gastrin-releasing peptide antagonists RC-3095 and RC- 3940-II

Zsuzsanna Kahán, Baodong Sun, Andrew V. Schally, José M. Arencibia, Ren Zhi Cai, Kate Groot, Gábor Halmos

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26 Scopus citations

Abstract

BACKGROUND. The growth of breast carcinoma is promoted by autocrine growth factors such as the bombesin (BN)-like peptides and epidermal growth factor (EGF). The stimulatory action of BN-like peptides can be blocked by the use of BN/gastrin-releasing peptide (GRP) antagonists. METHODS. The authors investigated the effects of synthetic BN/GRP antagonists RC-3095 and RC-3940-II on tumor growth and the expression of mRNA for EGF receptors and three BN receptor subtypes in MDA-MB-468 human breast carcinoma. Athymic nude mice with xenografts of MDA-MB-468 human breast carcinoma were injected subcutaneously for 6 weeks with RC-3940-II at doses of 20 or 40 μg/day. In another study, the effects of RC-3940-II and RC-3095 were compared. RESULTS. RC-3940-II caused a significant and dose-dependent growth inhibition of MDA- MB-468 tumors in nude mice; therapy with either dose of RC-3940-II significantly (P < 0.01) reduced the mean final tumor volume and weight compared with controls. RC-3940-II induced a persistent regression of > 50% of all tumors. One of 3 tumors treated with 20 μg of RC-3940-II and 3 of 5 tumors treated with 40 μg were found to have regressed completely by the end of the study. When RC-3940-II and RC-3095 were compared at the dose of 20 μg/day, both powerfully suppressed growth of MDA-MB-468 tumors, with RC- 3940-II causing a complete regression of 2 tumors and RC-3095 a complete regression of 1 tumor. Receptor analyses of untreated MDA-MB-468 tumors revealed an overexpression of EGF receptors and two classes of binding sites for BN/GRP. mRNAs for receptors of GRP, neuromedin B, and BN receptor subtype-3 were detected by reverse transcriptase-polymerase chain reaction. CONCLUSIONS. A virtual arrest of growth or regression of MDA-MB-468 human breast carcinoma after therapy with RC-3940-II and RC-3095 indicates that these BN/GRP antagonists could provide a new treatment modality for breast tumors expressing BN and EGF receptors. (C) 2000 American Cancer Society.

Original languageEnglish (US)
Pages (from-to)1384-1392
Number of pages9
JournalCancer
Volume88
Issue number6
DOIs
StatePublished - Mar 15 2000

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Keywords

  • Bombesin
  • Estrogen-independent breast carcinoma
  • Gastrin-releasing peptide (GRP) antagonists

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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