title: Vinblastine, Vincristine and Vindesine: anti-invasive effect on MO4 mouse fibrosarcoma cells in vitro.
abstract: Inhibition of the invasiveness of MO4 mouse fibrosarcoma cells by the vinca alkaloid, vinblastine (VLB), vincristine (VCR) and vindesine (VDS), has been examined in vitro. At doses between 0.006 microgram/ml (minimal effect) and 0.1 microgram/ml (complete inhibition) these drugs interfered with the invasion of MO4 cells from an aggregate confronting a fragment of embryonic chick heart in three-dimensional culture. We have also examined the effect of these drugs on the following activities of MO4 cells: growth, directional migration and assembly of the cytoplasmic microtubule complex. Growth and directional migration were affected by the same doses of vinca alkaloids as invasion. In contrast with the vinca alkaloids, 5-fluorouracil at 1 microgram/ml inhibited growth but allowed directional migration and invasion. At a dose of 0.3 microgram/ml VLB, VCR and VDS interfered with the assembly of cytoplasmic microtubules, as visible after immunocytochemical staining with tubulin antiserum. Ultrastructural analysis demonstrated that inhibition of invasion in three-dimensional culture corresponds with abolishment of the cytoplasmic microtubule complex. Anti-invasive concentrations of VLB, VCR and VDS represent clinically achievable plasma concentrations. We concluded that the anti-invasive effect of the vinca alkaloids may contribute to their antitumor activity.
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D008809:Mice, Inbred C3H; D008870:Microtubules / Q000187:drug effects; D009361:Neoplasm Invasiveness / Q000648:ultrastructure*; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology / Q000648:ultrastructure; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014751:Vindesine
chemical_list: D014747:Vinblastine; D014751:Vindesine