Smith J P, Solomon T E
Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey.
Gastroenterology. 1988 Dec;95(6):1541-8. doi: 10.1016/s0016-5085(88)80075-1.
The effects of gastrin, proglumide (a gastrin receptor antagonist), and somatostatin on growth of human colon adenocarcinoma cell lines CX1, X56, and HT29 were examined in two experimental models. Nude mice bearing xenografts of colon cancer CX1 or X56 were treated for 14-25 days subcutaneously with saline, pentagastrin (0.5 or 1.0 mg/kg), proglumide (250 or 500 mg/kg), or somatostatin 14 (33, 100, or 300 micrograms/kg) twice daily. Tumor volume, weight, protein, and deoxyribonucleic acid were measured. HT29 cells were grown in vitro and the effects of gastrin 17, proglumide, and somatostatin on growth were evaluated by cell counts or [3H]thymidine incorporation. The larger dose of pentagastrin significantly increased tumor growth in the nude mouse (p less than 0.005) and gastrin induced a biphasic effect on deoxyribonucleic acid synthesis in tissue culture with significant increases of up to 39% (p less than 0.025). Somatostatin alone significantly inhibited tumor growth in two of the cell lines and also inhibited the gastrin-induced growth. Proglumide had no effect by itself but significantly inhibited gastrin-stimulated growth. These findings suggest that growth of some human colon cancers may be hormone-dependent.
在两种实验模型中研究了胃泌素、丙谷胺(一种胃泌素受体拮抗剂)和生长抑素对人结肠腺癌细胞系CX1、X56和HT29生长的影响。将荷有结肠癌CX1或X56异种移植物的裸鼠,每日皮下注射两次生理盐水、五肽胃泌素(0.5或1.0mg/kg)、丙谷胺(250或500mg/kg)或生长抑素14(33、100或300μg/kg),持续14 - 25天。测量肿瘤体积、重量、蛋白质和脱氧核糖核酸。HT29细胞在体外培养,通过细胞计数或[³H]胸腺嘧啶核苷掺入法评估胃泌素17、丙谷胺和生长抑素对生长的影响。较大剂量的五肽胃泌素显著增加裸鼠的肿瘤生长(p < 0.005),胃泌素对组织培养中的脱氧核糖核酸合成产生双相效应,最高显著增加39%(p < 0.025)。单独使用生长抑素显著抑制两种细胞系中的肿瘤生长,并且还抑制胃泌素诱导的生长。丙谷胺本身无作用,但显著抑制胃泌素刺激的生长。这些发现表明,某些人类结肠癌的生长可能是激素依赖性的。