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 |
| |
Authors: | Sinisa Radulovic Andrew V. Schally Herta Reile Gabor Halmos Karoly Szepeshazi Kate Groot Slobodan Milovanovic Glenn Miller Tetsu Yano |
| |
Affiliation: | a Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, Louisiana, USAb Department of Medicine, Tulane University Medical School, New Orleans, Louisiana, USA |
| |
Abstract: | 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 μg/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 μg had the greatest and consistently significant inhibitory effect on tumor growth. RC-3095 given once daily s.c. at a dose of 20 μg 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. |
| |
Keywords: | |
本文献已被 InformaWorld 等数据库收录! |
|