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 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.
Litvak
D A
DA
Department of Surgery, University of Texas Medical Branch, Galveston 77555-0527, USA.
Hellmich
M R
MR
Iwase
K
K
Evers
B M
BM
Martinez
J
J
Amblard
M
M
Townsend
C M
CM
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005755:Gastrins / Q000037:antagonists & inhibitors*; D006801:Humans; D006965:Hyperplasia; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009930:Organic Chemicals; D011498:Protein Precursors / Q000037:antagonists & inhibitors*; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D005755:Gastrins; C118848:JMV 1155; D009930:Organic Chemicals; D011498:Protein Precursors; D011949:Receptors, Cholecystokinin; C013706:big gastrin