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  • Title: Anti-gastric cancer effects of celecoxib, a selective COX-2 inhibitor, through inhibition of Akt signaling.
    Author: Kim N, Kim CH, Ahn DW, Lee KS, Cho SJ, Park JH, Lee MK, Kim JS, Jung HC, Song IS.
    Journal: J Gastroenterol Hepatol; 2009 Mar; 24(3):480-7. PubMed ID: 18823436.
    Abstract:
    BACKGROUND AND AIM: Previously, we showed that treatment with celecoxib significantly reduced the number of viable gastric cancer cells, in a dose- and time-dependent manner. However, the specific anti-cancer effects of celecoxib on gastric cancer cells have not been clarified. The present in vitro study was carried out to investigate the mechanism involved in the anti-gastric cancer effects of celecoxib. METHODS: 3-(4,5-Dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was carried out after treating AGS cells (human gastric cancer cell line, ATCC CRL 1739) with celecoxib or indomethacin, and the effect of prostaglandin E(2) or LY294002 (PI3K inhibitor) was evaluated. Western blot analysis of tAkt (total Akt), pAkt (phosphorylated Akt), pGSK3beta (phosphorylated glycogen synthase kinase-3beta), pFKHR (phosphorylated forkhead transcriptional factor), and caspase-9 was carried out at various concentrations (0, 5, 10, 25, or 50 micromol/L) of celecoxib or indomethacin-treatment for 24 or 48 h in AGS cells. RESULTS: Celecoxib- or LY294002-induced cell death was found to occur in a dose-dependent manner in AGS cells, and these decreases were slightly recovered by the addition of PGE(2) (25 or 50 micromol/L). The expression of pAkt but not tAkt was lower in the celecoxib treated-AGS cells and the response was dose dependent (P < 0.05). The expression of pGSK3beta and pFKHR was also significantly decreased in the celecoxib treated-AGS cells. Procaspase 9 (47 kDa) was frequently cleaved into 37, 35 and 17 kDa fragments in the celecoxib-treatment group. However, these changes in cell signal transduction were not observed in the indomethacin treated-AGS cells. CONCLUSION: The anti-cancer effects of celecoxib on gastric cancer cells might be partly mediated by downregulation of Akt, GSK3beta, FKHR, and upregulation of caspase-9, in the mitochondrial apoptotic pathway.
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