Effects of prostaglandin E(2) on proliferation and apoptosis of epithelial ovarian cancer cells.
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 E(2) (dmPGE(2)) at increasing concentrations of 0-10 microg/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 dmPGE(2) 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 E(2) 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.
Munkarah
A R
AR
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, 4707 St. Antoine -5 West, Detroit, MI 48201, USA.
Morris
R
R
Baumann
P
P
Deppe
G
G
Malone
J
J
Diamond
M P
MP
Saed
G M
GM
D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D051546:Cyclooxygenase 2; D017931:DNA Primers; D015232:Dinoprostone / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020287:In Situ Nick-End Labeling; D007527:Isoenzymes / Q000235:genetics; D007700:Kinetics; D008565:Membrane Proteins; D010051:Ovarian Neoplasms / Q000473:pathology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D017931:DNA Primers; D007527:Isoenzymes; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone