Alexander R W, Upp J R, Poston G J, Townsend C M, Singh P, Thompson J C
Department of Surgery, University of Texas Medical Branch, Galveston 77550.
Pancreas. 1988;3(3):297-302. doi: 10.1097/00006676-198805000-00010.
Bombesin, a 14-amino acid peptide, exhibits direct and indirect effects on the gastrointestinal tract, including release of hormones, stimulation of pancreatic, gastric, and intestinal secretion and intestinal motility. Cholecystokinin (CCK) and gastrin, two of the hormones released by bombesin, have been shown to play a role in maintaining the growth of normal gastrointestinal mucosa as well as in eliciting trophic responses in normal and neoplastic tissue. We studied the effects of chronic bombesin treatment on the growth of a human ductal pancreatic adenocarcinoma (SKI) xenografted into nude mice, and on the growth of the normal nude mouse pancreas. Thirteen nude mice were implanted with SKI tumor and divided into two groups. Mice received 0.1 ml intraperitoneal injections of either bombesin (20 micrograms/kg) or the vehicle alone three times per day. Tumor areas were measured twice weekly until death (week 8), at which time the tumors and the host pancreas were excised, weighed, and assayed for protein, RNA, and DNA content. Significant inhibition of tumor growth was found in the bombesin-treated group at weeks 4, 5, 6, 7, and 8. Tumor area and weight at death (day 57) were significantly less in the bombesin-treated group (48 and 46%) as compared with control. We observed similar inhibition of tumor DNA (39%), RNA (38%), and protein (43%) content compared with controls. In contrast, bombesin significantly increased the weight (64%), protein (81%), and DNA (73%) content of the mouse pancreas compared with controls. We conclude that bombesin acts concurrently as both a trophic agent for normal host pancreas and a growth inhibitory agent in xenografted pancreatic cancer tissue.
蛙皮素是一种含14个氨基酸的肽,对胃肠道具有直接和间接作用,包括激素释放、刺激胰腺、胃和肠道分泌以及肠道蠕动。蛙皮素释放的两种激素——胆囊收缩素(CCK)和胃泌素,已被证明在维持正常胃肠道黏膜生长以及在正常组织和肿瘤组织中引发营养反应方面发挥作用。我们研究了长期给予蛙皮素对移植到裸鼠体内的人胰腺导管腺癌(SKI)生长以及对正常裸鼠胰腺生长的影响。13只裸鼠植入SKI肿瘤并分为两组。小鼠每天接受3次腹腔注射,每次0.1 ml,注射的要么是蛙皮素(20微克/千克),要么是单独的赋形剂。每周两次测量肿瘤面积,直至死亡(第8周),此时切除肿瘤和宿主胰腺,称重,并检测蛋白质、RNA和DNA含量。在第4、5、6、7和8周时,发现蛙皮素治疗组的肿瘤生长受到显著抑制。与对照组相比,蛙皮素治疗组在死亡时(第57天)的肿瘤面积和重量显著更小(分别为48%和46%)。与对照组相比,我们观察到肿瘤DNA(39%)、RNA(38%)和蛋白质(43%)含量也受到类似抑制。相反,与对照组相比,蛙皮素显著增加了小鼠胰腺的重量(64%)、蛋白质(81%)和DNA(73%)含量。我们得出结论,蛙皮素同时作为正常宿主胰腺的营养因子和异种移植胰腺癌组织中的生长抑制因子发挥作用。