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

Background: 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. Methods: DLD-1 cells (2 x 10⁶) were injected subcutaneously (sc) at a single site in athymic nude mice. Mice were randomized to four groups (n = 6/group) to receive injections, sc, 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. Results: 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%). Conclusions: 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.