title: Effects of camptothecin on tumor cell proliferation and angiogenesis when coupled to a bombesin analog used as a targeted delivery vector.
abstract: The camptothecin-bombesin conjugate termed DC-51-43, as a novel targeted drug delivery system, was examined in over 10 human tumor cell lines and shows a potent antiproliferative activity. This conjugate has also demonstrated its antitumor activity in our previous experiments. In our present study, we evaluate this conjugate for its antiangiogenic activity by in-vitro and in-vivo experiments. The camptothecin-bombesin conjugate and free camptothecin show potent in-vitro inhibitory activities of cell adhesion to various extracellular matrix components and integrins alphaVbeta3 and alphaVbeta5, not beta1/alphabeta1. This conjugate displays inhibitory activity to cell migration and invasion at concentrations of 10 micromol/l or above. This conjugate is also effective against in-vitro capillary-like tube formation of endothelial cells (at 40 micromol/l), and in-vivo angiogenesis as seen by blocking the spread of host mice endothelial cells into matrigel plugs. These experimental results support the fact that the camptothecin-bombesin conjugate has therapeutic activities against angiogenesis. By binding to bombesin receptor-expressing sites, this bombesin analog, consisting of 11 amino acids, is potentially a novel delivery vector for nonspecific cytotoxic agents.
authors.affiliation: Peptide Research Laboratories, Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112, USA. lsun@tulane.edu
authors.forename: Li-Chun
authors.initials: LC
authors.lastname: Sun
authors.forename: Jing
authors.initials: J
authors.lastname: Luo
authors.forename: Vienna L
authors.initials: VL
authors.lastname: Mackey
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Fuselier
authors.forename: David H
authors.initials: DH
authors.lastname: Coy
mesh_terms: D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001839:Bombesin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002166:Camptothecin / Q000494:pharmacology*; D002448:Cell Adhesion; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D016023:Integrins / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology; D016192:Resting Phase, Cell Cycle / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D016023:Integrins; D001839:Bombesin; D002166:Camptothecin