title: Effects of the synthetic vasopressin analog desmopressin in a mouse model of colon cancer.
abstract: Experimental and clinical data indicated that perioperative administration of the hemostatic peptide desmopressin (DDAVP) can inhibit progression of residual metastatic cells. The compound seems to act by inducing an agonist effect on specific V2 vasopressin membrane receptors present in both tumor cells and endothelial cells. Here we explored the antitumor effects of DDAVP in cultured colon carcinoma cells and in a syngeneic Balb/c mouse model. Both human Colo-205 and mouse CT-26 colon carcinoma cell lines expressed the V2 receptor, as revealed by immunofluorescence. DDAVP (at doses ranging from 100 ng/ml to 1 μg/ml) exerted a modest but significant antiproliferative effect on cultured CT-26 and Colo-205 cells. In vivo, DDAVP (2 intravenous doses of 2 μg/kg) reduced accumulation of ascites and formation of intestinal tumor nodules in mice intraperitoneally inoculated with CT-26 cells. Perioperative administration of DDAVP significantly inhibited tumor progression in animals surgically implanted in the spleen with CT-26 cells, and caused some reduction in liver metastasis. Although DDAVP and 5-fluorouracil demonstrated additive cytostatic effects in vitro, no antitumor effects were observed in this study in mice receiving a single cycle of chemotherapy (25 mg/kg) in combination with the peptide. Our data suggest that DDAVP may be potentially used to minimize spread or survival of residual malignant cells during surgical procedures for colon and other gastrointestinal tumors.
authors.affiliation: Laboratory of Molecular Oncology, Department of Science and Technology, Quilmes National University, Buenos Aires, Argentina.
authors.forename: Giselle V
authors.initials: GV
authors.lastname: Ripoll
authors.forename: Juan
authors.initials: J
authors.lastname: Garona
authors.forename: Guillermo A
authors.initials: GA
authors.lastname: Hermo
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Gomez
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Alonso
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017483:Receptors, Vasopressin / Q000096:biosynthesis
chemical_list: D000970:Antineoplastic Agents; D017483:Receptors, Vasopressin; D003894:Deamino Arginine Vasopressin