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Obstetrics & Gynecology 2002;100:677-682
© 2002 by The American College of Obstetricians and Gynecologists
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ORIGINAL RESEARCH

Aspirin-Induced Inhibition of Ovarian Tumor Cell Growth

Janet G. Drake, MD and Jeanne L. Becker, PhD

From the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of South Florida College of Medicine, Tampa, Florida.

Address reprint requests to: Janet G. Drake, MD, East Tennessee State University, James H. Quillen College of Medicine, Department of Obstetrics and Gynecology, PO Box 70569, Johnson City, TN 37614; E-mail: drake{at}etsu.edu.

OBJECTIVE: To determine if aspirin inhibits the growth of ovarian tumor cells in vitro and to investigate possible mechanisms involved in inhibition.

METHODS: OVCAR-3 ovarian tumor cells were grown in monolayer cultures and then harvested for use in proliferation assays. The cells were then treated with vehicle (1% absolute ethanol), 1–5-mmol/L aspirin, 1-µg/mL of anti HER-2/neu monoclonal antibody, or 20-ng/mL heregulin, the ligand for the HER-2/neu receptor either alone or in combination. Cellular proliferation was determined spectrophotometrically by the reduction of tetrazolium dye. Expression of Her-2/neu was assessed by flow cytometry.

RESULTS: Aspirin induced inhibition of OVCAR-3 tumor cell growth in a dose-dependent fashion ranging from little to no inhibitory response in cultures treated with 1-mmol/L aspirin to 68% in those treated with 5-mmol/L aspirin. Expression of HER-2/neu was likewise reduced in a dose-dependent manner from 87% expression in control cells to 16% in those treated with 5-mmol/L aspirin. Addition of heregulin alone resulted in 23% proliferation over the control. The combination of heregulin plus 2-mmol/L aspirin caused 66% inhibition of tumor cell growth, whereas the blocking of the HER-2/neu receptor with the monoclonal antibody resulted in an even greater inhibitory response of 82%.

CONCLUSION: OVCAR-3 tumor cell growth is inhibited by aspirin, and suppression appears to be potentiated by blocking the HER-2/neu receptor.




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