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

Eur J Cancer. 1998 Apr;34(5):710-7. doi: 10.1016/s0959-8049(97)10123-x.

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 micrograms 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Blotting, Southern
  • Bombesin / analogs & derivatives*
  • Bombesin / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Division / drug effects
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Peptide Fragments / therapeutic use*
  • Polymerase Chain Reaction / methods
  • RNA, Messenger / metabolism
  • Radioimmunoassay
  • Receptors, Bombesin
  • Receptors, Cholecystokinin / metabolism
  • Transplantation, Heterologous

Substances

  • Antineoplastic Agents
  • Peptide Fragments
  • RNA, Messenger
  • Receptors, Bombesin
  • Receptors, Cholecystokinin
  • bombesin(6-14), Hca(6)-Leu(13)-psi(CH2N)-Tac(14)-
  • bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-
  • ErbB Receptors
  • Bombesin