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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

Inhibition of Cyclooxygenase-2 Decreases DNA Synthesis Induced by Platelet-Derived Growth Factor in Swiss 3T3 Fibroblasts

Esther Castaño, Ramon Bartrons and Joan Gil
Journal of Pharmacology and Experimental Therapeutics May 2000, 293 (2) 509-513;
Esther Castaño
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Ramon Bartrons
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Joan Gil
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Abstract

NS-398 [N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide], a selective inhibitor of cyclooxygenase-2 (COX-2), inhibited proliferation induced by platelet-derived growth factor (PDGF) in Swiss 3T3 fibroblasts. The effect of NS-398 was found to be concentration-dependent. The half-maximal effect occurred at ∼0.1 μM. NS-398 decreased mitogenesis at subsaturating PDGF concentrations and the inhibitory effect of NS-398 was overcome by increasing PDGF concentration. SC-236, another COX-2 selective inhibitor, also inhibited PDGF-induced proliferation. In contrast, two selective COX-1 inhibitors, valeryl salicylate and ketorolac, had no significant inhibitory effect on PDGF-stimulated DNA synthesis. The inhibition was obtained when NS-398 was added during the first hour after PDGF addition. At 1 h, PDGF induced COX-2 protein and prostaglandin (PG)E2 synthesis, and NS-398 blocked the synthesis of PGE2. The inhibitory effect of NS-398 on PDGF-stimulated DNA synthesis was counteracted by 280 nM PGE2. The antimitogenic action of NS-398 and SC-236 suggests that selective inhibition of COX-2 may produce antiproliferative effects with substantial safety advantages over nonselective COX inhibitors.

Footnotes

  • Send reprint requests to: Dr. Joan Gil, Unitat de Bioquı́mica, Departament de Ciències Fisiòlogiques II, Campus de Bellvitge, Universitat de Barcelona, PabellóCentral, 4a planta, C/Feixa Llarga s/n, 08907 Hospitalet de Ll, Barcelona, Spain. E-mail: joangil{at}bellvitge.bvg.ub.es

  • ↵1 This study was supported by grants from Comisión Interministerial de Ciencia y Tecnologı́a (SAF98-0100) and Marató de TV3.

  • Abbreviations:
    NSAID
    nonsteroidal anti-inflammatory drug
    COX
    cyclooxygenase
    PG
    prostaglandin
    NS-398
    N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
    SC-236
    4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
    PDGF
    platelet-derived growth factor
    VSA
    valeryl salicylate
    FCS
    fetal calf serum
    DMEM
    Dulbecco's modified Eagle's medium
    TBST
    Tris-buffered saline/Tween 20
    NF-κB
    nuclear factor-κB
    • Received August 11, 1999.
    • Accepted January 10, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 293 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 293, Issue 2
1 May 2000
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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

Inhibition of Cyclooxygenase-2 Decreases DNA Synthesis Induced by Platelet-Derived Growth Factor in Swiss 3T3 Fibroblasts

Esther Castaño, Ramon Bartrons and Joan Gil
Journal of Pharmacology and Experimental Therapeutics May 1, 2000, 293 (2) 509-513;

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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

Inhibition of Cyclooxygenase-2 Decreases DNA Synthesis Induced by Platelet-Derived Growth Factor in Swiss 3T3 Fibroblasts

Esther Castaño, Ramon Bartrons and Joan Gil
Journal of Pharmacology and Experimental Therapeutics May 1, 2000, 293 (2) 509-513;
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