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 colorectal cancer cells and to investigate the mechanisms by which aspirin might 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. Analysis of cell-cycle distribution and bcl-2 expression was assessed by flow cytometry.


RESULTS
Acetylsalicylic acid induced a dose-dependent inhibition of Ishikawa cells in vitro. The percentage of growth inhibition was 21-88% at concentrations 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 treated with the lowest concentration of ASA exhibited 2% apoptosis and more than 60% of the population expressed bcl-2. Apoptosis levels increased as levels of ASA increased from 2 to 5 mM (7-58%) with a concommitant decrease in bcl-2 expression from 46% at 2 mM to 2% at 5 mM. Acetylsalicylic acid concentrations of 3 mM or greater induced a shift from the resting phase (G0/G1) to S phase of the cell cycle.


CONCLUSIONS
Acetylsalicylic acid inhibited Ishikawa cell growth in vitro in a dose-dependent manner. Apoptosis is one of the mechanisms involved in the response, which can be mediated in part by downregulation of bcl-2.
Arango
H A
HA
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of South Florida College of Medicine, Tampa, Florida, USA.
Icely
S
S
Roberts
W S
WS
Cavanagh
D
D
Becker
J L
JL
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016889:Endometrial Neoplasms / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D019253:Proto-Oncogene Proteins c-bcl-2; D001241:Aspirin