Co-inhibition of cyclooxygenase-2 and dihydropyrimidine dehydrogenase by non-steroidal anti-inflammatory drugs in tumor cells and xenografts

Andrea Réti, Éva Pap, A. Zalatnai, A. Jeney, Judit Kralovánszky, Barna Budai

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) may be able to enhance the antitumor effect of cancer drugs. Cyclooxygenase-2 (COX-2) is the best characterized target of NSAIDs. It was demonstrated that elevated dihydropyrimidine dehydrogenase (DPD) and COX-2 activities influence the response to 5-fluorouracil (5-FU). We previously showed that NSAIDs increased 5-FU sensitivity only in high COX-2-expressing cancer cells. Materials and Methods: The effect of indomethacin and NS-398 on DPD activity and mRNA expression in a high COX-2-expressing (determined by Western blotting, immunoflourescence and immunohistochemistry) cell line (24-, 48-hour, 10-day treatment) and xenograft (3-week treatment) was investigated. Results: The coexistence of high COX-2 and DPD activity or low activities of both enzymes were detected. After treatment with NSAIDs, a simultaneous and significant decrease of both activities was also demonstrated. Conclusion: NSAIDs could be promising modulators of fluorouracil-based chemotherapy, especially in high COX-2-expressing tumours.

Original languageEnglish
Pages (from-to)3095-3101
Number of pages7
JournalAnticancer Research
Volume29
Issue number8
Publication statusPublished - Aug 2009

Fingerprint

Dihydrouracil Dehydrogenase (NADP)
Cyclooxygenase 2
Heterografts
Anti-Inflammatory Agents
Fluorouracil
Pharmaceutical Preparations
Neoplasms
Indomethacin
Therapeutics
Western Blotting
Immunohistochemistry
Drug Therapy
Cell Line
Messenger RNA
Enzymes

Keywords

  • COX-2
  • DPD
  • HCA-7
  • HT-29
  • NSAIDs

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Co-inhibition of cyclooxygenase-2 and dihydropyrimidine dehydrogenase by non-steroidal anti-inflammatory drugs in tumor cells and xenografts. / Réti, Andrea; Pap, Éva; Zalatnai, A.; Jeney, A.; Kralovánszky, Judit; Budai, Barna.

In: Anticancer Research, Vol. 29, No. 8, 08.2009, p. 3095-3101.

Research output: Contribution to journalArticle

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AU - Kralovánszky, Judit

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