Aspirin effects on endometrial cancer cell growth

Objective: To find whether aspirin (acetylsalicylic acid, ASA) inhibits the growth of endometrial cancer cells in vitro in a way similar to that in co lorectal cancer cells and to investigate the mechanisms by which aspirin mi ght lead to growth inhibition. Methods: Ishikawa human endometrial tumor cells were grown in the presence of ASA (1-5 mM) for 96 hours. Controls were treated with vehicle (absolute ethanol). Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl) - 2,5-diphenyltetrazolium bromide assay. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. Analys is of cell-cycle distribution and bcl-2 expression was assessed by flow cyt ometry. Results: Acetylsalicylic acid induced a dose-dependent inhibition of Ishika wa tells in vitro. The percentage of growth inhibition was 21-88% at concen trations of 1-5 mM. It also induced apoptosis and reduced bcl-2 expression in Ishikawa cells in a dose-dependent manner. Control cells and cells treat ed with the lowest concentration of ASA exhibited 2% apoptosis and more tha n 60% of the population expressed bcl-2 Apoptosis levels increased as level s of ASA increased from 2 to 5 mM (7-58%) with a concommitant decrease in b cl-2 expression from 46% at 2 mM to 2% at 5 mM. Acetylsalicylic acid concen trations of 3 mM or greater induced a shift from the resting phase (G0/G1) to S phase of the cell cycle. Conclusion: Acetylsalicylic acid inhibited Ishikawa cell growth in vitro in a dose-dependent manner. Apoptosis is one of the mechanisms involved in th e response, which can be mediated in part by downregulation of bcl-2. (C) 2 001 by The American College of Obstetricians and Gynecologists.