title: Inhibition of growth of colon 38 adenocarcinoma by vinblastine and colchicine: evidence for a vascular mechanism.
abstract: Vinblastine or colchicine, administered intraperitoneally to B6D2F1 mice with advanced subcutaneous colon 38 tumours, induced substantial tumour growth delays with progressive development of haemorrhagic necrosis beginning within 8 hours of treatment. Two multidrug-resistant P388 leukaemia sublines, refractory to vinblastine and vincristine when grown as intraperitoneal ascites, were sensitive to necrosis induction when grown as subcutaneous tumours. Vascular labelling with two fluorescent markers indicated that vincristine substantially reduced tumour blood flow within 4 hours after treatment. The effects of vinblastine, vincristine and colchicine were similar to those of tumour necrosis factor alpha in that: (a) similar tumour necrosis and blood flow changes were induced, (b) coadministration of the serotonin antagonist cyproheptidine prevented tumour necrosis and (c) plasma nitrate levels were elevated, indicative of the stimulation of oxidation of L-arginine to nitric oxide. The results suggest that vinca alkaloids and colchicine act on solid tumours by host cell-mediated vascular effects as well as by direct tubulin-mediated cytotoxicity.
authors.affiliation: Cancer Research Laboratory, University of Auckland Medical School, New Zealand.
authors.forename: B C
authors.initials: BC
authors.lastname: Baguley
authors.forename: K M
authors.initials: KM
authors.lastname: Holdaway
authors.forename: L L
authors.initials: LL
authors.lastname: Thomsen
authors.forename: L
authors.initials: L
authors.lastname: Zhuang
authors.forename: L J
authors.initials: LJ
authors.lastname: Zwi
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D003078:Colchicine / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D004351:Drug Resistance; D007942:Leukemia, Experimental / Q000188:drug therapy; D051379:Mice; D008815:Mice, Inbred Strains; D009336:Necrosis / Q000139:chemically induced; D009566:Nitrates / Q000097:blood; D014747:Vinblastine / Q000627:therapeutic use*
chemical_list: D009566:Nitrates; D014747:Vinblastine; D003078:Colchicine