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ORIGINAL RESEARCH |
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), 15-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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