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

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

Research output: Contribution to journalArticle

24 Citations (Scopus)

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
Pages (from-to)1384-1392
Number of pages9
JournalCancer
Volume88
Issue number6
DOIs
Publication statusPublished - Mar 15 2000

Fingerprint

Gastrin-Releasing Peptide
Bombesin
Estrogens
Breast Neoplasms
Growth
Neoplasms
Nude Mice
Bombesin Receptors
Cholecystokinin B Receptor
Hca(6)-Leu(13)-psi(CH2N)-Tac(14)-bombesin(6-14)
Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-bombesin (6-14)
Messenger RNA
Peptides
Reverse Transcriptase Polymerase Chain Reaction
Epidermal Growth Factor
Heterografts
Intercellular Signaling Peptides and Proteins
Binding Sites

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Inhibition of growth of MDA-MB-468 estrogen-independent human breast carcinoma by bombesin/gastrin-releasing peptide antagonists RC-3095 and RC- 3940-II. / Kahán, Z.; Sun, Baodong; Schally, Andrew V.; Arencibia, José M.; Cai, Ren Zhi; Groot, Kate; Halmos, Gábor.

In: Cancer, Vol. 88, No. 6, 15.03.2000, p. 1384-1392.

Research output: Contribution to journalArticle

Kahán, Z. ; Sun, Baodong ; Schally, Andrew V. ; Arencibia, José M. ; Cai, Ren Zhi ; Groot, Kate ; Halmos, Gábor. / Inhibition of growth of MDA-MB-468 estrogen-independent human breast carcinoma by bombesin/gastrin-releasing peptide antagonists RC-3095 and RC- 3940-II. In: Cancer. 2000 ; Vol. 88, No. 6. pp. 1384-1392.
@article{5c7c294ad9b54a6999488ce5b0061272,
title = "Inhibition of growth of MDA-MB-468 estrogen-independent human breast carcinoma by bombesin/gastrin-releasing peptide antagonists RC-3095 and RC- 3940-II",
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.",
keywords = "Bombesin, Estrogen-independent breast carcinoma, Gastrin-releasing peptide (GRP) antagonists",
author = "Z. Kah{\'a}n and Baodong Sun and Schally, {Andrew V.} and Arencibia, {Jos{\'e} M.} and Cai, {Ren Zhi} and Kate Groot and G{\'a}bor Halmos",
year = "2000",
month = "3",
day = "15",
doi = "10.1002/(SICI)1097-0142(20000315)88:6<1384::AID-CNCR16>3.0.CO;2-Q",
language = "English",
volume = "88",
pages = "1384--1392",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "6",

}

TY - JOUR

T1 - Inhibition of growth of MDA-MB-468 estrogen-independent human breast carcinoma by bombesin/gastrin-releasing peptide antagonists RC-3095 and RC- 3940-II

AU - Kahán, Z.

AU - Sun, Baodong

AU - Schally, Andrew V.

AU - Arencibia, José M.

AU - Cai, Ren Zhi

AU - Groot, Kate

AU - Halmos, Gábor

PY - 2000/3/15

Y1 - 2000/3/15

N2 - 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.

AB - 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.

KW - Bombesin

KW - Estrogen-independent breast carcinoma

KW - Gastrin-releasing peptide (GRP) antagonists

UR - http://www.scopus.com/inward/record.url?scp=0034653403&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034653403&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1097-0142(20000315)88:6<1384::AID-CNCR16>3.0.CO;2-Q

DO - 10.1002/(SICI)1097-0142(20000315)88:6<1384::AID-CNCR16>3.0.CO;2-Q

M3 - Article

VL - 88

SP - 1384

EP - 1392

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 6

ER -