Cyclooxygenase-2 inhibitor nimesulide suppresses telomerase activity by blocking Akt/PKB activation in gastric cancer cell line.. Yu Baoping; Hu Guoyong; Yu Jieping; Ran Zongxue; Luo Hesheng (2004) Digestive diseases and sciences display abstract
Nonsteroidal antiinflammatory drugs (NSAIDs) have been reported to have antiproliferative effects in neoplastic cells of different origin during the past few decades. We aimed to study the effects of the selective COX-2 inhibitor, nimesulide, on cell viability and telomerase and Akt/PKB activity in the human gastric cancer cell line MKN-45 and to explore the molecular mechanism for the antitumor activity of the selective COX-2 inhibitor. We tested the influence of nimesulide on the gastric cancer cell line MKN-45 in vitro. Trypan blue exclusion was used to determine the cell viability after incubation for 0, 12, 24, and 48 hr in different concentrations of nimesulide 0, 25, 50, 100, 200 microM). After treatment or no treatment with 100 microM nimesulide for 0, 12, 24, or 48 hr in the presence or absence of 300 nM okadaic acid for 2 hr, telomerase and Akt/PKB activity was measured using TRAP PCR-ELISA and nonradioactive IP kinase assays, respectively. In the gastric cancer cell line MKN-45 nimesulide caused a time- and dose-dependent reduction in cell numbers and significantly inhibited telomerase and Akt/PKB activity; the inhibition of telomerase activity was partly associated with the attenuation of Akt/PKB activity. These results demonstrate that the selective COX-2 inhibitor suppresses the telomerase activity of gastric cancer cells, in part by blocking the activation of protein kinase B, which provides a new signaling mechanism responsible for the anticancer effects of the selective COX-2 inhibitor.