Aspirin-induced inhibition of ovarian tumor cell growth.

Abstract

To determine if aspirin inhibits the growth of ovarian tumor cells in vitro and to investigate possible mechanisms involved in inhibition. 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-microg/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. 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%. OVCAR-3 tumor cell growth is inhibited by aspirin, and suppression appears to be potentiated by blocking the HER-2/neu receptor.