Therapeutic effect of the gastrin receptor antagonist, CR2093 on gastrointestinal tumour cell growth.
Therapeutic effect of the gastrin receptor antagonist, CR2093 on gastrointestinal tumour cell growth.
复制标题
胃蛋白受体拮抗剂的治疗作用，CR2093对胃肠道肿瘤细胞生长。
DOI：
10.1038/bjc.1992.184
复制
发表时间：
1992-06
影响因子：
8.8
通讯作者：
Hardcastle, J D
中科院分区：
文献类型：
--
作者：
Watson, S A;Crosbee, D M;Morris, D L;Robertson, J F;Makovec, F;Rovati, L C;Hardcastle, J D
胃泌素受体拮抗剂CR 2093与125 I-胃泌素-17竞争（5 x 10（-10）M），用于与大鼠胰腺癌上的胃泌素受体结合，AR 42 J（CR2093浓度诱导50%的125 I-胃泌素-17结合（IC 50）为8 × 10（-5）M），对人胃腺癌，MKN 45（IC 50 5.5 × 10 - 5 M）和人结肠直肠腺癌C523（IC 50大于10 - 4 M）。CR2093的静脉内施用（40 mg kg-1天-1）将胃泌素-17刺激的裸鼠中AR 42 J异种移植物的生长降低至低于原始基础生长的生长（来自基础的P = 0.0166和来自胃泌素刺激的生长的P = 0.0109）。CR2093给药也降低了MKN 45异种移植物的胃泌素刺激的生长（P = 0.045），但未能抑制C523异种移植物的胃泌素增强的增殖。这可能与异种移植物系上存在的胃泌素受体的亲和力（Kd）有关，因为CR 2093抑制的两种异种移植物的Kd分别为4.6 x 10（-10）M（AR 42 J）和1.2 x 10（-9）M（MKN 45），而C523的Kd具有更高的亲和力（2.2 x 10（-10）M）。GR拮抗剂可能是胃泌素受体阳性胃肠道肿瘤的一种可行的治疗选择。
The gastrin receptor antagonist, CR2093, competed with 125I-gastrin-17 (5 x 10(-10) M) for binding to gastrin receptors on the rat pancreatic adenocarcinoma, AR42J (CR2093 concentration inducing 50% of 125I-gastrin-17 binding (IC50) was 8 x 10(-5) M), on the human gastric adenocarcinoma, MKN45 (IC50 5.5 x 10(-5) M) and the human colo-rectal adenocarcinoma C523 (IC50 greater than 10(-4) M). Intravenous administration of CR2093 (40 mg kg-1 day-1) reduced the gastrin-17 stimulated growth of AR42J xenografts in nude mice to below that of the original basal growth (P = 0.0166 from basal and P = 0.0109 from gastrin stimulated growth). CR2093 administration also reduced the gastrin-stimulated growth of MKN45 xenografts (P = 0.045) but failed to inhibit the gastrin enhanced proliferation of C523 xenografts. This may be related to the affinity (Kd) of the gastrin receptors present on the xenograft lines as the Kds of the two xenografts inhibited by CR2093 were 4.6 x 10(-10) M (AR42J) and 1.2 x 10(-9) M (MKN45) respectively whereas the Kd of C523 was of higher affinity (2.2 x 10(-10) M). GR antagonists may be a viable therapeutic option for gastrin receptor positive, gastro-intestinal tumours.