The Anti-Cancer Effect of COX-2 Inhibitors on Gastric Cancer Cells

Abstract

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.

Anticancer Effect of Celecoxib via COX-2 Dependent and Independent Mechanisms in Human Gastric Cancers Cells

“…Another study showed that the anticancer effects of celecoxib on gastric carcinoma cells appear to be mediated by cell-cycle arrest and apoptosis, and not by COX-2 or PGE2 suppression alone [21]. The effect of celecoxib on AGS cell survival was evaluated in the present study, we found that the survival rate of AGS treated with celecoxib or COX-2-specific RNA interference (RNAi), or both celecoxib and COX-2-specific RNAi, was much lower than that of AGS control.…”

Epiregulin: Roles in normal physiology and cancer

“…However, there are also reports that amphiregulin or epiregulin stimulate PGE 2 production by stimulating cyclooxygenase 2 expression [72]. Either of these mechanisms may account for the suppression of gastric tumor growth in vivo and for the inhibition of gastric tumor cell line proliferation in vitro by COX-2 inhibitors [73, 74]. …”

Celecoxib Inhibits β-Catenin-Dependent Survival of the Human Osteosarcoma MG-63 Cell Line

“…13 -15 In particular, celecoxib has been shown to act as an inhibitor of proliferation in several tumour cell types. 16,17 The antitumour effects of celecoxib depend on its COX-2-inhibiting potency, i.e. its regulation of the prostaglandin pathways.…”