The combined effects of proglumide and fluorouracil on the growth of murine Colon 38 cancer cells in vitro.
The role of gastrins and their receptors in the pathogenesis of colon cancer has been discussed for many years but it still remains unresolved. Although fluorouracil (FU) remains to be reference chemotherapy for colon cancer, its efficacy is unsatisfactory. Recently, we have shown a synergistic effect of proglumide (a non-selective blocker of cholecystokinin-gastrin receptors) applied together with FU, on the proliferation and apoptosis of transplantable Colon 38 cancer cells in vivo. The aim of this study was to examine direct effects of proglumide (10(-5)-10(-10) M) applied either alone or together with FU (0.25, 2.5 and 25 microg/ml) on the proliferation of murine Colon 38 cancer cells in vitro. Cell proliferation was assessed by the modified colorimetric Mosmann method. Proglumide inhibited the proliferation of Colon 38 cells at the concentrations of 10(-6), 10(-8) and 10(-10) M. FU inhibited the proliferation of cancer cells in all studied concentrations, exerting the most profound antiproliferative effect at the concentrations of 2.5 and 25 microg/ml. Thus, the former concentration was chosen to study its interactions with proglumide. Proglumide applied together with FU exerted a synergistic effect on the inhibition of proliferation of Colon 38 cells at 10(-8), 10(-9), 10(-10) M concentrations. The most profound inhibitory effect was observed in the group incubated with FU and 10(-10) M of proglumide. The obtained results indicate a possibility of new therapeutic options for colon cancer, but further studies are needed to elucidate, if the synergistic effect of FU and proglumide occurs also in the colon cancer in humans.
Mełeń-Mucha
Gabriela
G
Department of Immunoendocrinology, Medical University of Łódź, Poland. g.m-mucha@wp.pl
Ławnicka
Hanna
H
Mucha
Sławomir
S
D000704:Analysis of Variance; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005472:Fluorouracil / Q000008:administration & dosage*; D066298:In Vitro Techniques; D051379:Mice; D011377:Proglumide / Q000008:administration & dosage*; D014407:Tumor Cells, Cultured
D011377:Proglumide; D005472:Fluorouracil