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 biosynthe tic precursor to gastrin (G-17), stimulates growth of some gastrointestinal cancers in vitro. The purpose of this study was twofold: to evaluate the e ffects 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-m ediated growth. Methods: DLD-1 cells (2x10(6)) were injected subcutaneously (sc) at a single site in athymic node mice. Mice were randomized to four g roups (n=6/group) to receive injections, sc, tid of either saline (control) , C-17-Gly, JMV1155, or G-17-Gly + JMV1155 for 28 days. Tumors were measure d biweekly until sacrifice at which time tumors were weighed and analyzed f or DNA and protein content Results: JMV1155 significantly inhibited G-17-Gl y-stimulated growth of DLD-1 rumors 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 fi rst rime, that the novel gastrin-receptor antagonist JMV1155, blocks G-17-G ly-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.