JMV1155: a novel inhibitor of glycine-extended progastrin-mediated growth of a human colon cancer in vivo.

Glycine-extended progastrin (G-17-Gly), the immediate biosynthetic precursor to gastrin (G-17), stimulates growth of some gastrointestinal cancers in vitro. The purpose of this study was twofold: to evaluate the effects of G-17-Gly on a human colon cancer (DLD-1) in vivo and to determine whether the novel gastrin-receptor antagonist, JMV1155, inhibits G-17-Gly-mediated growth. DLD-1 cells (2 x 10(6)) were injected subcutaneously (s.c.) at a single site in athymic nude mice. Mice were randomized to four groups (n = 6/group) to receive injections, s.c., tid of either saline (control), G-17-Gly, JMV1155, or G-17-Gly + JMV1155 for 28 days. Tumors were measured biweekly until sacrifice at which time tumors were weighed and analyzed for DNA and protein content. JMV1155 significantly inhibited G-17-Gly-stimulated growth of DLD-1 tumors by 14 days of treatment, producing a 56% decrease in tumor size by 28 days. JMV1155 also significantly decreased G-17-Gly-mediated increases in tumor weight (by 64%), DNA content (by 61%), and protein content (by 65%). We have demonstrated, for the first time, that the novel gastrin-receptor antagonist, JMV1155, blocks G-17-Gly-induced growth of a transplanted human colon cancer in vivo. Hormonally based therapy with JMV1155 potentially could be employed for some patients with colon carcinoma.

Citation

D A Litvak, M R Hellmich, K Iwase, B M Evers, J Martinez, M Amblard, C M Townsend. JMV1155: a novel inhibitor of glycine-extended progastrin-mediated growth of a human colon cancer in vivo. Anticancer research. 1999 Jan-Feb;19(1A):45-9

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PMID: 10226523

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