Synergistic inhibition effect of tumor growth by using celecoxib in combination with oxaliplatin

Cancer Invest. 2009 Jul;27(6):636-40. doi: 10.1080/07357900802672738.

Abstract

Background: To evaluate the effects of celecoxib, in combination with oxaliplatin, on tumour growth, cell apoptosis and angiogenesis in nude mice models.

Materials and methods: Xenograft mice model of colon cancer was established using the BALB/c nude mice. Medicine was administered respectively in different groups. Tumour volumes, the expression level of survivin, beta-catenin, VEGF mRNA level, the microvessel density and cell apoptosis were measured.

Results: Celecoxib, oxaliplatin and combination use caused a tumour inhibition of 35%, 31% and 63% respectively. Compared with control group, a significant redation of angiogenesis and the levels of COX-2, survivin and beta-cantenin protein, and increase of cell apoptosis were detected in tumors in celecoxib group. Celecoxib in combination with oxaliplatin could further promote cell apoptosis and reduce beta-catenin protein expression.

Conclusion: Celecoxib could inhibit tumor growth and enhance the antitumor effects of oxaliplatin through their synergistic role in inhibiting different targets.

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects
  • Celecoxib
  • Cell Proliferation / drug effects*
  • Colonic Neoplasms / blood supply
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / enzymology
  • Colonic Neoplasms / pathology
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Drug Synergism
  • HT29 Cells
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microtubule-Associated Proteins / metabolism
  • Neovascularization, Pathologic / prevention & control
  • Organoplatinum Compounds / pharmacology
  • Oxaliplatin
  • Pyrazoles / pharmacology
  • RNA, Messenger / metabolism
  • Sulfonamides / pharmacology
  • Survivin
  • Vascular Endothelial Growth Factor A / metabolism
  • Xenograft Model Antitumor Assays
  • beta Catenin / metabolism

Substances

  • BIRC5 protein, human
  • CTNNB1 protein, human
  • Cyclooxygenase 2 Inhibitors
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Organoplatinum Compounds
  • Pyrazoles
  • RNA, Messenger
  • Sulfonamides
  • Survivin
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • beta Catenin
  • Oxaliplatin
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Celecoxib