Therapeutic effect of the gastrin receptor antagonist, CR2093 on gastrointestinal tumour cell growth View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

1992-06

AUTHORS

S A Watson, D M Crosbee, D L Morris, J F Robertson, F Makovec, L C Rovati, J D Hardcastle

ABSTRACT

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. More... »

PAGES

879

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/bjc.1992.184

DOI

http://dx.doi.org/10.1038/bjc.1992.184

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1028579012

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/1616859


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