neuropeptide-y and 2--5--dideoxyadenosine

We investigated the effect of neuropeptides, which are vasoactive intestinal polypeptide (VIP), substance P, (SP), neuropeptide Y (NPY), neurokinin A (NKA), somatostatin (SOM), calcitonin gene-related peptide (CGRP), and leucine-enkephalin (L-ENK), on the invasion of murine Colon 26-L5 adenocarcinoma cells through a reconstituted basement membrane (Matrigel) using a Transwell cell culture chamber assay. VIP, SP, NPY, and L-ENK reduced invasive potential of tumor cells in a concentration-dependent manner, whereas SOM, CGRP, and NKA had no effect. Especially, VIP showed the most effective in inhibiting tumor invasion, and achieved 50% reduction at 10(-6) M. A similar effect by VIP was also observed in cell migration to fibronectin. VIP had no effect on the growth of tumor cells at the concentrations ranging from 10(-10) to 10(-6) M. The suppressed ability of the tumor cell motility by VIP (10(-6) M) was practically recovered by co-treatment with 2',5'-dideoxyadenosine, an adenylate cyclase inhibitor. These results indicate that VIP, among the neuropeptides used, could inhibit Matrigel invasion of Colon 26-L5 carcinoma cells through partial suppression of their motility, and the reduction was associated with an intracellular cAMP-mediated pathway.

Topics: Adenocarcinoma; Animals; Biocompatible Materials; Calcitonin Gene-Related Peptide; Cell Division; Cell Movement; Colforsin; Collagen; Colonic Neoplasms; Dideoxyadenosine; Dose-Response Relationship, Drug; Drug Combinations; Enkephalins; Laminin; Leucine; Mice; Neoplasm Invasiveness; Neurokinin A; Neuropeptide Y; Neuropeptides; Proteoglycans; Somatostatin; Substance P; Tumor Cells, Cultured; Vasoactive Intestinal Peptide