Inhibitory effect of bombesin/gastrin-releasing peptide (GRP) antagonists RC-3950-II and RC-3095 on MCF-7 MIII human breast cancer xenografts in nude mice.
Bombesin/gastrin-releasing peptide (GRP) may be involved in the growth of human breast cancers. Nude mice bearing xenografts of MCF-7 MIII human breast cancer cell line were treated for 7 weeks with bombesin/GRP antagonists RC-3950-II and RC-3095. RC-3950-II, administered sc twice daily at a dose of 10 micrograms, produced significant inhibitory effects on tumor growth after 2 weeks of administration. RC-3095 acetate (D 22213), injected sc twice daily at the same dose of 10 micrograms, suppressed tumor growth after 4 weeks. Both RC-3950-II and RC-3095 significantly decreased the final tumor volume and tumor weights. RC-3950-II appeared to be somewhat more efficacious than RC-3095 in inhibiting the growth of MCF-7 MIII breast cancers. Chronic treatment with either bombesin/GRP antagonist caused down-regulation of receptors for epidermal growth factor (EGF) in tumor cell membranes, which might be related to inhibition of tumor growth. These findings suggest that bombesin/GRP antagonists should be considered for a new endocrine therapy of breast cancer.
Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, LA 70146.
Y
Y
Shirahige
R Z
RZ
Cai
K
K
Szepeshazi
G
G
Halmos
J
J
Pinski
K
K
Groot
A V
AV
Schally
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001839:Bombesin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015536:Down-Regulation; D066246:ErbB Receptors; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D010446:Peptide Fragments; C071363:bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-; D066246:ErbB Receptors; D001839:Bombesin