Effects of prostaglandin E2 on proliferation and apoptosis of epithelial ovarian cancer cells

A. R. Munkarah, R. Morris, P. Baumann, G. Deppe, J. Malone, Michael Peter Diamond, G. M. Saed

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Objective: There is strong evidence indicating that prostaglandins (PG) and their synthesizing enzyme cyclooxygenase-2 (COX-2) play an important role in tumorigenesis. The purposes of the present study were to determine the pattern of expression of COX-2 and the effect of PG treatment on proliferation and apoptosis in epithelial ovarian cancer cells. Methods: Two epithelial ovarian cancer cell lines, MDAH-2774 and SKOV3, were grown in flasks to confluence. Cells were then treated with exogenous dimethyl prostaglandin E2 (dmPGE2) at increasing concentrations of 0-10 μg/mL. Total RNA was extracted from cells at different treatment doses and subjected to reverse transcriptase-polymerase chain reaction for the semiquantitative analysis of COX-2, Bcl-2, and bax expression. Flow cytometry was performed to assess effect of treatment on the cell cycle. The TUNEL assay was used to assess apoptosis. Results: We found that COX-2 was constitutively expressed in the MDAH-2774 and SKOV3 epithelial ovarian cancer cells as determined by detection of a 304-bp amplified fragment using specific primers for the COX-2 gene. Treatment of both cell lines with dmPGE2 resulted in dose-dependently higher expression of COX-2, Bcl-2, and bax mRNA compared with untreated cells. These changes were associated with an increase in the proliferative fraction and with a simultaneous reduction in apoptosis. Conclusions: Prostaglandin E2 stimulated proliferation and reduced apoptosis in epithelial ovarian cancer cells. These effects were associated with overexpression of COX-2 and an increase in the ratio of Bcl-2:bax mRNA.

Original languageEnglish (US)
Pages (from-to)168-173
Number of pages6
JournalJournal of the Society for Gynecologic Investigation
Volume9
Issue number3
DOIs
StatePublished - May 21 2002

Fingerprint

Cyclooxygenase 2
Dinoprostone
Apoptosis
Prostaglandins
Cell Line
Messenger RNA
In Situ Nick-End Labeling
Ovarian epithelial cancer
Reverse Transcriptase Polymerase Chain Reaction
Cell Cycle
Flow Cytometry
Carcinogenesis
RNA
Enzymes
Genes

Keywords

  • Apoptosis
  • Ovarian cancer
  • Prostaglandins

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Effects of prostaglandin E2 on proliferation and apoptosis of epithelial ovarian cancer cells. / Munkarah, A. R.; Morris, R.; Baumann, P.; Deppe, G.; Malone, J.; Diamond, Michael Peter; Saed, G. M.

In: Journal of the Society for Gynecologic Investigation, Vol. 9, No. 3, 21.05.2002, p. 168-173.

Research output: Contribution to journalArticle

Munkarah, A. R. ; Morris, R. ; Baumann, P. ; Deppe, G. ; Malone, J. ; Diamond, Michael Peter ; Saed, G. M. / Effects of prostaglandin E2 on proliferation and apoptosis of epithelial ovarian cancer cells. In: Journal of the Society for Gynecologic Investigation. 2002 ; Vol. 9, No. 3. pp. 168-173.
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AU - Malone, J.

AU - Diamond, Michael Peter

AU - Saed, G. M.

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N2 - Objective: There is strong evidence indicating that prostaglandins (PG) and their synthesizing enzyme cyclooxygenase-2 (COX-2) play an important role in tumorigenesis. The purposes of the present study were to determine the pattern of expression of COX-2 and the effect of PG treatment on proliferation and apoptosis in epithelial ovarian cancer cells. Methods: Two epithelial ovarian cancer cell lines, MDAH-2774 and SKOV3, were grown in flasks to confluence. Cells were then treated with exogenous dimethyl prostaglandin E2 (dmPGE2) at increasing concentrations of 0-10 μg/mL. Total RNA was extracted from cells at different treatment doses and subjected to reverse transcriptase-polymerase chain reaction for the semiquantitative analysis of COX-2, Bcl-2, and bax expression. Flow cytometry was performed to assess effect of treatment on the cell cycle. The TUNEL assay was used to assess apoptosis. Results: We found that COX-2 was constitutively expressed in the MDAH-2774 and SKOV3 epithelial ovarian cancer cells as determined by detection of a 304-bp amplified fragment using specific primers for the COX-2 gene. Treatment of both cell lines with dmPGE2 resulted in dose-dependently higher expression of COX-2, Bcl-2, and bax mRNA compared with untreated cells. These changes were associated with an increase in the proliferative fraction and with a simultaneous reduction in apoptosis. Conclusions: Prostaglandin E2 stimulated proliferation and reduced apoptosis in epithelial ovarian cancer cells. These effects were associated with overexpression of COX-2 and an increase in the ratio of Bcl-2:bax mRNA.

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