Inhibitory effects of antagonists of bombesin/gastrin releasing peptide (GRP) and somatostatin analog (RC-160) on growth of HT-29 human colon cancers in nude mice.
Nude mice bearing xenografts of HT-29 human colon cancer cell line were treated for 4 weeks with somatostatin analog (RC-160), bombesin/gastrin releasing peptide (GRP) antagonists (RC-3095 and RC-3440). In three separate experiments somatostatin analog RC-160 (50 micrograms/day) released from microgranules significantly reduced tumor growth. Bombesin/GRP antagonists, RC-3095 and RC-3440 injected subcutaneously (s.c.) twice daily at a dose of 10 micrograms had the greatest and consistently significant inhibitory effect on tumor growth. RC-3095 given once daily s.c. at a dose of 20 micrograms was less effective. RC-3095 also inhibited metastatic tumor growth after intrasplenic injection of HT-29 cells in nude mice. Specific binding sites of somatostatin, bombesin and epidermal growth factor (EGF) were detected on intact HT-29 cells or on the membranes from HT-29 tumor xenografts. The inhibitory effects of bombesin antagonists on tumor growth were consistently linked with a significant down-regulation of EGF receptors. Bombesin/GRP antagonists and somatostatin analogs could be considered for the development of new hormonal therapies for colon cancer.
Radulovic
S
S
Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, LA 70146.
Schally
A V
AV
Reile
H
H
Halmos
G
G
Szepeshazi
K
K
Groot
K
K
Milovanovic
S
S
Miller
G
G
Yano
T
T
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001839:Bombesin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000378:metabolism; D019886:Gastrin-Releasing Peptide; D005755:Gastrins / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000037:antagonists & inhibitors*; D011869:Radioligand Assay; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D005755:Gastrins; D010446:Peptide Fragments; D010455:Peptides; C071363:bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-; C090517:bombesin(6-14), Tpi(6)-Leu(13)-psi(CH2N)-Tpi(14)-; C051458:vapreotide; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D019886:Gastrin-Releasing Peptide; D013006:Growth Hormone; D066246:ErbB Receptors; D001839:Bombesin