SOMATOSTATIN ANALOG RC-160 AND BOMBESIN GASTRIN-RELEASING PEPTIDE ANTAGONIST RC-3095 INHIBIT THE GROWTH OF ANDROGEN-INDEPENDENT DU-145 HUMAN PROSTATE-CANCER LINE IN NUDE-MICE

Nude mice bearing xenografts of the androgen-independent human prostate cancer DU-145 were treated for 4-5 weeks with somatostatin analog RC-160 or the bombesin/gastrin-releasing peptide (GRP) antagonist RC-3095. Tumor growth in animals treated with somatostatin analog RC-160 at a dose of 100 mug/day s.c. was significantly inhibited within 14 days of the start of the experiment. At necropsy, in mice given RC-160, tumor weight and volume were significantly decreased compared with control mice. Treatment with RC-3095 at a dose of 20 mug/day s.c. also suppressed tumor growth, the inhibition being significant after 2 weeks, but the reduction in tumor volume and weight was smaller than that produced by RC-160. Therapy with RC-160 significantly decreased serum growth hormone and gastrin levels. Specific binding sites for bombesin, somatostatin and epidermal growth factor (EGF) were found in the DU-145 tumor membranes. Receptors for EGF were significantly down-regulated after therapy with RC-3095 and RC-160. The finding that somatostatin analog RC-160 and bombesin/GRP antagonist RC-3095 inhibit the growth of androgen-independent prostate tumors in mice might be of practical importance for human prostate cancer therapy.