title: Enhanced Anti-Angiogenic Effect of Low Molecular Weight Heparin-Bile Acid Conjugates by Co-Administration of a Selective COX-2 Inhibitor.
abstract: OBJECTIVE
  To overcome definite limitations of angiogenesis inhibitors such as insufficient therapeutic efficacy as a single drug and resisting or conflicting effect under chronic treatment, it is required to develop a new regimen to improve the therapeutic effect.
  
  
  METHODS
  The combination effect of a multi-targeting angiogenesis inhibitor (LHT7) and a selective cyclooxygenase-2 inhibitor (celecoxib) on neovascularization in tumor growth was studied both in vitro and vivo experiments.
  
  
  RESULTS
  While hypoxia-mediated COX-2 overexpression and macrophage recruitment were observed at LHT7-treated tumor tissues, it was well-controlled by the combination of celecoxib and LHT7. On the other hand, the in vitro tube formation and the in vivo tumor vessel formation and structure were inhibited by either LHT7 or celecoxib, but the inhibition effect was further enhanced by using them together. However, the combination therapy did not further enhance the inhibitory effect on tumor growth in terms of volume compared to single drug uses, which attributed not to increased cellular apoptosis but to decreased cell proliferation.
  
  
  CONCLUSIONS
  COX-2 inhibition could enhance the therapeutic effect of anti-angiogenic drugs both by inhibiting the inflammatory reactions induced by hypoxia and by altering the vascular stabilization that is mediated by an assembly with mural cells.
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, 151-742, South Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Seung Woo
authors.initials: SW
authors.lastname: Chung
authors.forename: Sang Yoon
authors.initials: SY
authors.lastname: Kim
authors.forename: Youngro
authors.initials: Y
authors.lastname: Byun
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000068579:Celecoxib / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015687:Cell Hypoxia / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D008815:Mice, Inbred Strains; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013656:Taurocholic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D052246:Cyclooxygenase 2 Inhibitors; D006495:Heparin, Low-Molecular-Weight; C580866:LHT7 compound; D013656:Taurocholic Acid; D051546:Cyclooxygenase 2; D000068579:Celecoxib