Aspirin-induced inhibition of ovarian tumor cell growth.
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-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.


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%.


CONCLUSIONS
OVCAR-3 tumor cell growth is inhibited by aspirin, and suppression appears to be potentiated by blocking the HER-2/neu receptor.
Drake
Janet G
JG
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of South Florida College of Medicine, Tampa, Florida, USA. drake@etsu.edu
Becker
Jeanne L
JL
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D020890:Neuregulin-1 / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001241:Aspirin; D020890:Neuregulin-1; D018719:Erb-b2 Receptor Tyrosine Kinases