Celecoxib reduces microvessel density in patients treated with nasopharyngeal carcinoma and induces changes in gene expression

Ross A. Soo, J. Wu, A. Aggarwal, Q. Tao, W. Hsieh, T. Putti, K. B. Tan, W. L. Soon, Y. F. Lai, B. Mow, S. Hsu, K. S. Loh, L. Tan, P. Tan, B. C. Goh

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Celecoxib is a selective cyclooxygenase-2 inhibitor with antitumor and antiangiogenic activity. We sought to determine pharmacodynamic change in tumors of patients with nasopharyngeal carcinoma (NPC) treated with celecoxib. Methods: Tumor biopsies were obtained before and after treatment with celecoxib 400 mg b.i.d. for 14 days in patients with newly diagnosed, untreated NPC. Tumor angiogenesis and cell proliferation were assessed by immunohistochemistry and gene expression by microarray analysis. Plasma celecoxib concentrations were obtained on days 8 and 14. Results: Paired samples were analyzed in 15 patients. Microvessel density was reduced in post-treatment samples and mean celecoxib levels reached therapeutic levels. Thirty-five genes (27 down-regulated, eight up-regulated) were differentially expressed on microarray analysis (p < 0.001). Down-regulated genes included cell cycle regulation-related (cyclin-dependent kinase 2, YES1), transcription factor (TRIP-Br2), whereas the antigen processing and presentation-related gene HLA-DM B was up-regulated. Conclusion: Celecoxib reduced angiogenesis and induced tumor transcriptional changes. Further characterization of these transcriptional changes in vivo is needed to provide further insights into the effects of celecoxib in neoplastic tissue. Our findings provide a rationale for clinical studies aimed at assessing the efficacy of celecoxib in the treatment of NPC.

Original languageEnglish (US)
Pages (from-to)1625-1630
Number of pages6
JournalAnnals of Oncology
Volume17
Issue number11
DOIs
StatePublished - Nov 2006

Keywords

  • Antiangiogenesis
  • Celecoxib
  • Gene expression
  • Nasopharyngeal carcinoma

ASJC Scopus subject areas

  • Hematology
  • Oncology

Fingerprint

Dive into the research topics of 'Celecoxib reduces microvessel density in patients treated with nasopharyngeal carcinoma and induces changes in gene expression'. Together they form a unique fingerprint.

Cite this