Pinski J, Halmos G, Schally A V
Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, Louisiana 70146.
Cancer Lett. 1993 Jul 30;71(1-3):189-96. doi: 10.1016/0304-3835(93)90115-p.
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 micrograms/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 micrograms/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.
将雄激素非依赖性人前列腺癌DU - 145异种移植瘤的裸鼠，用生长抑素类似物RC - 160或蛙皮素/胃泌素释放肽（GRP）拮抗剂RC - 3095治疗4 - 5周。以100微克/天的剂量皮下注射生长抑素类似物RC - 160治疗的动物，在实验开始后的14天内肿瘤生长受到显著抑制。尸检时，给予RC - 160的小鼠，其肿瘤重量和体积与对照小鼠相比显著降低。以20微克/天的剂量皮下注射RC - 3095治疗也抑制了肿瘤生长，2周后抑制作用显著，但肿瘤体积和重量的减小幅度小于RC - 160所产生的效果。用RC - 160治疗显著降低了血清生长激素和胃泌素水平。在DU - 145肿瘤细胞膜中发现了蛙皮素、生长抑素和表皮生长因子（EGF）的特异性结合位点。用RC - 3095和RC - 160治疗后，EGF受体显著下调。生长抑素类似物RC - 160和蛙皮素/GRP拮抗剂RC - 3095可抑制小鼠雄激素非依赖性前列腺肿瘤生长这一发现，可能对人类前列腺癌治疗具有实际意义。
