Inhibition of paclitaxel-induced apoptosis by the specific COX-2 inhibitor, NS398, in epithelial ovarian cancer cells

A. R. Munkarah, Z. Genhai, R. Morris, V. V. Baker, G. Deppe, Michael Peter Diamond, G. M. Saed

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Objective. In vitro studies have revealed that treatment of various human cancer cell lines with specific cyclo-oxygenase 2 (COX-2) inhibitors induces apoptotic cell death. It is currently proposed that the combination of COX-2 inhibitors with chemotherapeutic agents improves the efficacy of cancer treatment. Materials and methods. In this study we sought to determine the effects of combining paclitaxel and the COX-2 inhibitor NS398 on apoptosis of epithelial ovarian cancer (EOC) cells. Two EOC cell lines, SKOV3 and MDAH2774, were exposed to increasing concentrations of paclitaxel (0.1, 10, and 100 μM) and NS398 (10, 100 μM) as well as a combination of both drugs. Apoptosis was evaluated by the Tunel assay. The fluorescein-labeled DNA was visualized directly by fluorescence microscopy and quantitated by flow cytometry. Results. While NS398 did not significantly alter apoptosis of either EOC cell lines after 24 h of continuous exposure, treatment of both cell lines with paclitaxel resulted in a significant increase in the rate of apoptosis (60-70%). Concomitant treatment of both SKOV3 and MDAH2774 cells with paclitaxel and NS398 resulted in marked impairment of paclitaxel-induced apoptosis. Similarly, sequential treatment during which both cell lines were treated with NS398 for 4 h, triple-washed, and then exposed to paclitaxel for 24 h resulted in a significant inhibition of paclitaxel-induced apoptosis. Similar inhibition was seen when NS398 was replaced by aspirin. Conclusion. Combining COX-2 inhibitors and paclitaxel does not have an additive or synergistic tumoricidal effect. On the contrary, NS398 treatment markedly inhibited the apoptotic effects of paclitaxel in each of these two EOC cell lines.

Original languageEnglish (US)
Pages (from-to)429-433
Number of pages5
JournalGynecologic Oncology
Volume88
Issue number3
DOIs
StatePublished - Mar 1 2003
Externally publishedYes

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Cyclooxygenase Inhibitors
Paclitaxel
Apoptosis
Cell Line
Ovarian epithelial cancer
N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
Drug Combinations
Fluorescein
Fluorescence Microscopy
Aspirin
Neoplasms
Flow Cytometry
Cell Death
DNA

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

Inhibition of paclitaxel-induced apoptosis by the specific COX-2 inhibitor, NS398, in epithelial ovarian cancer cells. / Munkarah, A. R.; Genhai, Z.; Morris, R.; Baker, V. V.; Deppe, G.; Diamond, Michael Peter; Saed, G. M.

In: Gynecologic Oncology, Vol. 88, No. 3, 01.03.2003, p. 429-433.

Research output: Contribution to journalArticle

Munkarah, A. R. ; Genhai, Z. ; Morris, R. ; Baker, V. V. ; Deppe, G. ; Diamond, Michael Peter ; Saed, G. M. / Inhibition of paclitaxel-induced apoptosis by the specific COX-2 inhibitor, NS398, in epithelial ovarian cancer cells. In: Gynecologic Oncology. 2003 ; Vol. 88, No. 3. pp. 429-433.
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