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

Anticancer Res. Jan-Feb 1999;19(1A):45-9.

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 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.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Gastrins / antagonists & inhibitors*
  • Humans
  • Hyperplasia
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Organic Chemicals*
  • Protein Precursors / antagonists & inhibitors*
  • Receptors, Cholecystokinin / antagonists & inhibitors*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Gastrins
  • JMV 1155
  • Organic Chemicals
  • Protein Precursors
  • Receptors, Cholecystokinin
  • big gastrin