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

David A. Litvak, Mark R. Hellmich, Kazuhiro Iwase, B. Mark Evers, Jean Martinez, Muriel Amblard, Courtney M. Townsend

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)45-49
Number of pages5
JournalAnticancer Research
Volume19
Issue number1 A
StatePublished - Apr 20 1999

Keywords

  • Colon cancer
  • Gastrin-receptor antagonist
  • Glycine-extended progastrin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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