Enhancement of antitumor activity of docetaxel by celecoxib in lung tumors

Int J Cancer. 2006 Jan 15;118(2):396-404. doi: 10.1002/ijc.21325.


Our study investigates the effect of a highly selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib, on the cytotoxicity of docetaxel in nude mice bearing A549 tumor xenografts and elucidates the molecular mechanisms of the antitumor effect of this combination. Female nu/nu mice, xenografted with s.c. A549 tumors were treated with either celecoxib (150 mg/kg/day), docetaxel (10 mg/kg) or a combination of both. The tumor tissues were quantified for the induction of apoptosis, intratumor levels/expressions of prostaglandin E2 (PGE2), 15 deoxy prostaglandin J2 (15-d PGJ2), microsomal prostaglandin E synthase (mPGES) and cytoplasmic phospholipase A2 (cPLA2). The combination of celecoxib with docetaxel significantly inhibited the tumor growth (p < 0.03) as compared to celecoxib or docetaxel alone, decreased the levels of PGE2 by 10-fold and increased the 15-d PGJ2 levels by 4-fold as compared to control. The combination also enhanced the peroxisome proliferator-activated receptor (PPAR)-gamma expression, decreased the expression of cPLA2, mPGES and vascular endothelial growth factor (VEGF), but had no effect on the expression of COX-1 or COX-2 in tumor tissues. TUNEL staining of the tumor tissues showed a marked increase in the apoptosis in the combination group as compared to the celecoxib- or docetaxel-treated groups and this was associated with an increase in the intratumor p53 expression. In conclusion, the combination of celecoxib with docetaxel produces a greater antitumor effect in s.c. A549 tumors as compared to celecoxib or docetaxel alone and this effect is associated with concomitant alterations in the intratumor levels of PGE2 and 15-d PGJ2.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / pathology
  • Animals
  • Apoptosis / drug effects
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Celecoxib
  • Cyclooxygenase Inhibitors / pharmacokinetics
  • Cyclooxygenase Inhibitors / pharmacology*
  • Cyclooxygenase Inhibitors / therapeutic use*
  • Dinoprostone / biosynthesis
  • Drug Interactions
  • Female
  • In Situ Nick-End Labeling
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Nude
  • Pyrazoles / pharmacokinetics
  • Pyrazoles / pharmacology*
  • Pyrazoles / therapeutic use*
  • Sulfonamides / pharmacokinetics
  • Sulfonamides / pharmacology*
  • Sulfonamides / therapeutic use*
  • Transplantation, Heterologous


  • Cyclooxygenase Inhibitors
  • Pyrazoles
  • Sulfonamides
  • Celecoxib
  • Dinoprostone