Preoperative growth inhibition of human gastric adenocarcinoma treated with a combination of celecoxib and octreotide

Acta Pharmacol Sin. 2007 Nov;28(11):1842-50. doi: 10.1111/j.1745-7254.2007.00652.x.

Abstract

Aim: To gain insight into the histopathological responses and molecular targets in the inhibition of growth of human gastric cancer treated with celecoxib (a cyclooxygenase [COX]-2 inhibitor) combined with octreotide.

Methods: Seventy five patients with gastric cancer undergoing curative gastrectomy or extended resection were randomly divided into 3 groups. The apoptosis of tumor cells was measured by terminal deoxynucleotide transferase-mediated dUTP nick endlabeling (TUNEL) assay. Gastric cancer microvessel density (MVD) and the expression of COX-2 were evaluated by immunohistochemical staining. The expression of somatostatin receptor (SSTR)-2 was detected with the biomolecular interaction analysis system. The transcription of non-steroidal anti-inflammatory drug-activated gene (NAG)-1 was measured by RT-PCR.

Results: Compared with the control and celecoxib groups, more necrosis in the combination group was observed. The apoptotic rate in the combination group (7.06%+/-0.67%) was significantly higher than that in the control group (6.23%+/-1.29%, P<0.05). The MVD decreased considerably in the combination group. The upregulation of NAG-1 was displayed both in the celecoxib and combination groups. The positive rate of SSTR-2 in gastric cancers treated with celecoxib (48%) was significantly higher than that of control group (12%) after surgery (P<0.05).

Conclusion: Celecoxib combined with octreotide significantly promoted necrosis in gastric adenocarcinoma through the induction of apoptosis and the reduction of MVD. NAG-1 and SSTR-2 might be the molecular targets for celecoxib or octreotide.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Apoptosis / drug effects*
  • Celecoxib
  • Female
  • Humans
  • Male
  • Middle Aged
  • Octreotide / administration & dosage*
  • Octreotide / pharmacology
  • Pyrazoles / administration & dosage*
  • Pyrazoles / pharmacology
  • Receptors, Somatostatin / metabolism
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Sulfonamides / administration & dosage*
  • Sulfonamides / pharmacology

Substances

  • Pyrazoles
  • Receptors, Somatostatin
  • Sulfonamides
  • somatostatin receptor 2
  • Celecoxib
  • Octreotide