Effects of nonsteroidal anti-inflammatory agents (NSAIDs) on ovarian carcinoma cell lines: preclinical evaluation of NSAIDs as chemopreventive agents.
OBJECTIVE
Nonsteroidal anti-inflammatory agents may inhibit carcinogenesis in specific tissues including the colon, breast, and pancreas, and, hence, may prove to be effective chemopreventive agents. The purpose of this study was to investigate the cellular effects of acetylsalicylic acid (ASA), acetaminophen, and a COX-2 inhibitor (NS-398) on the growth of cell lines of human ovarian cancer in vitro.


METHODS
SK-OV-3, Caov-3, and NIH:OVCAR-3 ovarian carcinoma cell lines were treated with ASA (10(-6) M-10(-2) M), acetaminophen (10(-6) M-10(-2) M), and a COX-2 inhibitor (10(-6) M-10(-4) M) for 96 h. The number of viable cells was determined using a tetrazolium conversion assay. Immunohistochemical assessment was performed for alterations in expression of Ki-67, erbB-2, COX enzyme, and apoptosis in primary ovarian cancer cells using terminal deoxynucleotidyl transferase (Tdt)-mediated nick end labeling assay.


RESULTS
A decrease in cell number compared with controls was observed for all of the cell lines treated with ASA, acetaminophen, and COX-2 inhibitor by cell count and tetrazolium conversion assay. A significant decrease in Ki-67 compared with controls in the OVCAR-3 (P = 0.005) and SK-OV-3 (P = 0.007) cell lines after treatment with the COX-2 inhibitor was observed. We observed a decrease in mitotic activity compared with controls in each cell line after treatment with the COX-2 inhibitor. Apoptosis was observed in primary ovarian cancer cell culture treated with COX-2 inhibitor.


CONCLUSIONS
Our results suggest additional study for the use of nonsteroidal anti-inflammatory agents, specifically COX-2 inhibitors, as a strategy of chemoprevention for ovarian cancer.
Rodríguez-Burford
Cristina
C
Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Biostatistics Unit, The University of Alabama at Birmingham, Birmingham, Alabama 35213, USA.
Barnes
Mack N
MN
Oelschlager
Denise K
DK
Myers
Russell B
RB
Talley
Lynya I
LI
Partridge
Edward E
EE
Grizzle
William E
WE
D000082:Acetaminophen / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000494:pharmacology; D001706:Biopsy; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D051546:Cyclooxygenase 2; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008565:Membrane Proteins; D009578:Nitrobenzenes / Q000494:pharmacology; D009924:Organ Culture Techniques; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000082:Acetaminophen; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001241:Aspirin; D051546:Cyclooxygenase 2; D007527:Isoenzymes; D019394:Ki-67 Antigen; D008565:Membrane Proteins; D009578:Nitrobenzenes; D011451:Prostaglandin-Endoperoxide Synthases; D018719:Erb-b2 Receptor Tyrosine Kinases; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; C496540:PTGS2 protein, human