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Journal of the Society for Gynecologic Investigation, Vol. 9, No. 3, 168-173 (2002)
DOI: 10.1177/107155760200900309

Effects of Prostaglandin E2 on Proliferation and Apoptosis of Epithelial Ovarian Cancer Cells

A. R. Munkarah, MD

R. Morris, MD

P. Baumann, MD

G. Deppe, MD

J. Malone, MD

M. P. Diamond, MD

Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan

G. M. Saed, PhD

Department of Obsterics and Gnecology, Wayne State University, 4707 St. Antoine -5 West, Detroit, MI 48201. g.saed{at}wayne.edu

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 proligeration 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 prolifieration 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.

Key Words: Prostaglandins • ovarian cancer • apoptosis


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