Background: human colon cancer cells have been found to express gastrin receptors and a role for gastrin in the growth of colon cancer has been postulated. Both mouse colon cancers and colon carcinoma cell lines are stimulated to grow by gastrin. In the present study we investigated the effects of pentagastrin and the gastrin receptor antagonists proglumide, benzotript and CR 2093 on the growth and polyamine metabolism of the human colon carcinoma cells Caco-2 which, after a phase of active replication, spontaneously differentiate into mature enterocytes. Methods: cells were grown in Dulbecco's Modified Eagle's medium supplemented with 10% fetal calf serum or in serum- free medium containing pentagastrin and/or proglumide, benzotript or CR 2093. Cell growth was assessed by hemocytometric connting. After treatment, thymidine labeling index, ornithine decardoxylase activity and putrescine uptake were evaluated at different time-points. Results: pentagastrin markedly increased the rate of cell growth and the number of cells in S phase as well as ornithine decarboxylase activity and putrescine uptake. These effects were all prevented by the gastrin receptor antagonists, which reduced the rate of cell growth also in cells not stimulated by the hormone. Difluoromethylornithine, a specific and irreversible inhibitor of ornithine decarboxylase, prevented the proliferative stimulus of pentagastrin, its effect being abolished by putrescine. Pentagastrin and the gastrin receptor antagonists had no effect on differentiated Caco-2 cells. Conclusions: pentagastrin stimulates the growth of Caco-2 cells by increasing intracellular polyamine concentration through both enhanced synthesis and increased uptake; the gastrin receptor antagonists prevent these effects. The reduction of the rate of cell growth induced by proglumide, benzotript and CR 2093 observed even in cells not stimulated by pentagastrin may suggest an autocrine production of gastrin or gastrin-like peptides by Caco-2 cells.
|Number of pages||7|
|Journal||Cancer Journal (United States)|
|Publication status||Published - 1994|
- colon cancer
- ornithine decarboxylase
ASJC Scopus subject areas
- Cancer Research