Inhibition of growth of MDA-MB-231 human breast cancer xenografts in nude mice by bombesin/gastrin-releasing peptide (GRP) antagonists RC-3940-II and RC-3095

M. Miyazaki, N. Lamharzi, Andrew V Schally, G. Halmos, K. Szepeshazi, K. Groot, R. Z. Cai

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Bombesin or gastrin-releasing peptide (GRP) may act as autocrine growth factors and play a role in the initiation and progression of breast cancer. We investigated the effect of bombesin/GRP antagonists RC-3095 and RC-3940- II on the growth of the MDA-MB-231 oestrogen-independent human breast cancer cell line xenografted into female nude mice. Bombesin/GRP antagonists, RC- 3095 and RC-3940-II, were administered subcutaneously twice daily at a dose of 10 μg for 5 weeks. The growth of MDA-MB-231 tumours was inhibited during the treatment, as shown by a reduction in tumour volume. RC-3940-II and RC- 3095 significantly decreased the final tumour volume by 72.4% and 57.7%, respectively, and greatly reduced tumour weights. RC-3940-II also significantly increased tumour doubling time and appeared to be more effective than RC-3095 in inhibiting the growth of MDA-MB-231 breast cancers. Serum gastrin and insulin-like growth factor-I (IGF-I) levels in animals treated with RC-3095 or RC-3940-II showed no significant changes as compared with controls. There was a significant decrease in the number of binding sites for epidermal growth factor (EGF), as well as bombesin, in tumour cells after chronic treatment with RC-3095 or RC-3940-II, which might be related to inhibition of tumour growth. Reverse transcription polymerase chain reaction, followed by Southern blot analysis, also showed a reduction in the expression of mRNA for EGF receptors in the group treated with RC-3940-II. Our findings suggest that bombesin/GRP antagonists such as RC-3095 or RC-3940-II could be considered for endocrine therapy for oestrogen-independent breast cancers, but further investigations are necessary.

Original languageEnglish
Pages (from-to)710-717
Number of pages8
JournalEuropean Journal of Cancer
Volume34
Issue number5
DOIs
StatePublished - Apr 1 1998
Externally publishedYes

Fingerprint

Gastrin-Releasing Peptide
Bombesin
Heterografts
Nude Mice
Breast Neoplasms
Growth
Tumor Burden
Neoplasms
Estrogens
Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-bombesin (6-14)
Hca(6)-Leu(13)-psi(CH2N)-Tac(14)-bombesin(6-14)
Gastrins
Southern Blotting
Insulin-Like Growth Factor I
Epidermal Growth Factor
Reverse Transcription
Intercellular Signaling Peptides and Proteins
Binding Sites
Cell Line
Polymerase Chain Reaction

Keywords

  • Bombesin/GRP antagonists
  • Oestrogen-independent breast cancer
  • Tumour inhibition

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

Inhibition of growth of MDA-MB-231 human breast cancer xenografts in nude mice by bombesin/gastrin-releasing peptide (GRP) antagonists RC-3940-II and RC-3095. / Miyazaki, M.; Lamharzi, N.; Schally, Andrew V; Halmos, G.; Szepeshazi, K.; Groot, K.; Cai, R. Z.

In: European Journal of Cancer, Vol. 34, No. 5, 01.04.1998, p. 710-717.

Research output: Contribution to journalArticle

@article{f2fbcd4a4f2f4d419aa9acbf131a2b9c,
title = "Inhibition of growth of MDA-MB-231 human breast cancer xenografts in nude mice by bombesin/gastrin-releasing peptide (GRP) antagonists RC-3940-II and RC-3095",
abstract = "Bombesin or gastrin-releasing peptide (GRP) may act as autocrine growth factors and play a role in the initiation and progression of breast cancer. We investigated the effect of bombesin/GRP antagonists RC-3095 and RC-3940- II on the growth of the MDA-MB-231 oestrogen-independent human breast cancer cell line xenografted into female nude mice. Bombesin/GRP antagonists, RC- 3095 and RC-3940-II, were administered subcutaneously twice daily at a dose of 10 μg for 5 weeks. The growth of MDA-MB-231 tumours was inhibited during the treatment, as shown by a reduction in tumour volume. RC-3940-II and RC- 3095 significantly decreased the final tumour volume by 72.4{\%} and 57.7{\%}, respectively, and greatly reduced tumour weights. RC-3940-II also significantly increased tumour doubling time and appeared to be more effective than RC-3095 in inhibiting the growth of MDA-MB-231 breast cancers. Serum gastrin and insulin-like growth factor-I (IGF-I) levels in animals treated with RC-3095 or RC-3940-II showed no significant changes as compared with controls. There was a significant decrease in the number of binding sites for epidermal growth factor (EGF), as well as bombesin, in tumour cells after chronic treatment with RC-3095 or RC-3940-II, which might be related to inhibition of tumour growth. Reverse transcription polymerase chain reaction, followed by Southern blot analysis, also showed a reduction in the expression of mRNA for EGF receptors in the group treated with RC-3940-II. Our findings suggest that bombesin/GRP antagonists such as RC-3095 or RC-3940-II could be considered for endocrine therapy for oestrogen-independent breast cancers, but further investigations are necessary.",
keywords = "Bombesin/GRP antagonists, Oestrogen-independent breast cancer, Tumour inhibition",
author = "M. Miyazaki and N. Lamharzi and Schally, {Andrew V} and G. Halmos and K. Szepeshazi and K. Groot and Cai, {R. Z.}",
year = "1998",
month = "4",
day = "1",
doi = "10.1016/S0959-8049(97)10123-X",
language = "English",
volume = "34",
pages = "710--717",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Limited",
number = "5",

}

TY - JOUR

T1 - Inhibition of growth of MDA-MB-231 human breast cancer xenografts in nude mice by bombesin/gastrin-releasing peptide (GRP) antagonists RC-3940-II and RC-3095

AU - Miyazaki, M.

AU - Lamharzi, N.

AU - Schally, Andrew V

AU - Halmos, G.

AU - Szepeshazi, K.

AU - Groot, K.

AU - Cai, R. Z.

PY - 1998/4/1

Y1 - 1998/4/1

N2 - Bombesin or gastrin-releasing peptide (GRP) may act as autocrine growth factors and play a role in the initiation and progression of breast cancer. We investigated the effect of bombesin/GRP antagonists RC-3095 and RC-3940- II on the growth of the MDA-MB-231 oestrogen-independent human breast cancer cell line xenografted into female nude mice. Bombesin/GRP antagonists, RC- 3095 and RC-3940-II, were administered subcutaneously twice daily at a dose of 10 μg for 5 weeks. The growth of MDA-MB-231 tumours was inhibited during the treatment, as shown by a reduction in tumour volume. RC-3940-II and RC- 3095 significantly decreased the final tumour volume by 72.4% and 57.7%, respectively, and greatly reduced tumour weights. RC-3940-II also significantly increased tumour doubling time and appeared to be more effective than RC-3095 in inhibiting the growth of MDA-MB-231 breast cancers. Serum gastrin and insulin-like growth factor-I (IGF-I) levels in animals treated with RC-3095 or RC-3940-II showed no significant changes as compared with controls. There was a significant decrease in the number of binding sites for epidermal growth factor (EGF), as well as bombesin, in tumour cells after chronic treatment with RC-3095 or RC-3940-II, which might be related to inhibition of tumour growth. Reverse transcription polymerase chain reaction, followed by Southern blot analysis, also showed a reduction in the expression of mRNA for EGF receptors in the group treated with RC-3940-II. Our findings suggest that bombesin/GRP antagonists such as RC-3095 or RC-3940-II could be considered for endocrine therapy for oestrogen-independent breast cancers, but further investigations are necessary.

AB - Bombesin or gastrin-releasing peptide (GRP) may act as autocrine growth factors and play a role in the initiation and progression of breast cancer. We investigated the effect of bombesin/GRP antagonists RC-3095 and RC-3940- II on the growth of the MDA-MB-231 oestrogen-independent human breast cancer cell line xenografted into female nude mice. Bombesin/GRP antagonists, RC- 3095 and RC-3940-II, were administered subcutaneously twice daily at a dose of 10 μg for 5 weeks. The growth of MDA-MB-231 tumours was inhibited during the treatment, as shown by a reduction in tumour volume. RC-3940-II and RC- 3095 significantly decreased the final tumour volume by 72.4% and 57.7%, respectively, and greatly reduced tumour weights. RC-3940-II also significantly increased tumour doubling time and appeared to be more effective than RC-3095 in inhibiting the growth of MDA-MB-231 breast cancers. Serum gastrin and insulin-like growth factor-I (IGF-I) levels in animals treated with RC-3095 or RC-3940-II showed no significant changes as compared with controls. There was a significant decrease in the number of binding sites for epidermal growth factor (EGF), as well as bombesin, in tumour cells after chronic treatment with RC-3095 or RC-3940-II, which might be related to inhibition of tumour growth. Reverse transcription polymerase chain reaction, followed by Southern blot analysis, also showed a reduction in the expression of mRNA for EGF receptors in the group treated with RC-3940-II. Our findings suggest that bombesin/GRP antagonists such as RC-3095 or RC-3940-II could be considered for endocrine therapy for oestrogen-independent breast cancers, but further investigations are necessary.

KW - Bombesin/GRP antagonists

KW - Oestrogen-independent breast cancer

KW - Tumour inhibition

UR - http://www.scopus.com/inward/record.url?scp=0032055880&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032055880&partnerID=8YFLogxK

U2 - 10.1016/S0959-8049(97)10123-X

DO - 10.1016/S0959-8049(97)10123-X

M3 - Article

C2 - 9713279

AN - SCOPUS:0032055880

VL - 34

SP - 710

EP - 717

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

IS - 5

ER -