The anti-cancer effect of COX-2 inhibitors on gastric cancer cells.
Epidemiologic studies have shown that nonsteroidal anti-inflammatory drugs could reduce the risk of cancer development including gastric cancer. This study was performed to identify the antineoplastic mechanism in gastric cancer cells affected by celecoxib, a selective COX-2 inhibitor. MTT assay, ELISA for prostaglandin E(2) (PGE(2)), cell-cycle analyses, immunofluorescent staining, and flow cytometry were performed after treating human gastric cancer cell lines (AGS and MKN-45) with celecoxib or indomethacin. The viabilities of celecoxib-treated cells decreased in a dose- and time-dependent manner compared with indomethacin. Drop of PGE(2) levels was more prominent in the presence of indomethacin than in that of celecoxib. Celecoxib arrested the cell cycle in the G(0)-G(1) phase, which reduced cell numbers in the S phase. Moreover, celecoxib increased the apoptotic cell proportions, a 4-fold increase over control cells. The anticancer effects of celecoxib on gastric cancer cells appear to be mediated by cell-cycle arrest and apoptosis, and not by COX-2 or PGE(2) suppression alone.
Cho
Soo-Jeong
SJ
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
Kim
Nayoung
N
Kim
Joo Sung
JS
Jung
Hyun Chae
HC
Song
In Sung
IS
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D000068579:Celecoxib; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D008856:Microscopy, Fluorescence; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D013778:Tetrazolium Salts; D013844:Thiazoles
D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D000068579:Celecoxib; D015232:Dinoprostone