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/

Bombesin or gastrin-releasing peptide (GRP) may act as autocrine growt h 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. Bombe sin/GRP antagonists, RC-3095 and RC-3940-II, were administered subcuta neously twice daily at a dose of 10 mu g for 5 weeks. The growth of MD A-MB-231 tumours was inhibited during the treatment, as shown by a red uction in tumour volume. RC-3940-II and RC-3095 significantly decrease d the final tumour volume by 72.4% and 57.7%, respectively, and greatl y reduced tumour weights. RC-3940-II also significantly increased tumo ur doubling time and appeared to be more effective than RC-3095 in inh ibiting the growth of MDA-MB-231 breast cancers. Serum gastrin and ins ulin-like growth factor-I (IGF-I) levels in animals treated with RC-30 95 or RC-3940-II showed no significant changes as compared with contro ls. There was a significant decrease in the number of binding sites fo r epidermal growth factor (EGF), as well as bombesin, in tumour cells after chronic treatment with RC-3095 or RC-3940-II, which might be rel ated to inhibition of tumour growth. Reverse transcription polymerase chain reaction, followed by Southern blot analysis, also showed a redu ction in the expression of mRNA for EGF receptors in the group treated with RC-3940-II. Our findings suggest that bombesin/GRP antagonists s uch as RC-3095 or RC-3940-II: could be considered for endocrine therap y for oestrogen-independent breast cancers, but further investigations are necessary. (C) 1998 Elsevier Science Ltd. All rights reserved.