[Nimesulide, a selective cyclooxygenase-2 inhibitor inhibits telomerase activity by blocking activation of PKB in gastric cancer cell line].
OBJECTIVE
To study the effects of nimesulide, a selective COX-2 inhibitor, on cell viability, telomerase and PKB activities in human gastric cancer cell line SGC7901 and to explore its molecular mechanism of selective growth inhibition.


METHODS
MTT assay was used to determine cell viability after incubation for 0, 12, 24, and 48 h in different concentrations (0, 25, 50, 100, 200 micro mol/L) of nimesulide and/or okadaic acid (300 nmol/L). Telomerase and protein kinase B (PKB) activities were detected using TRAP PCR-ELISA and nonradioactive IP-kinase assay.


RESULTS
Nimsulide caused a time and dose-dependent reduction of cell numbers of SGC7901. The telomerase and PKB activities were significantly inhibited, and the inhibition of telomerase activity was partly associated with decrease in PKB activity.


CONCLUSIONS
Selective COX-2 inhibitor nimesulide inhibits telomerase activity of gastric cancer cells by partly blocking the activation of protein kinase B. The results suggest an additional signaling pathway underlying the anti-cancer effect of COX-2 inhibitor.
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Guo-yong
GY
Hu
Bao-ping
BP
Yu
Jie-ping
JP
Yu
Zong-xue
ZX
Ran
He-sheng
HS
Luo
D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology*; D019098:Telomerase / Q000378:metabolism*; D013997:Time Factors
D016861:Cyclooxygenase Inhibitors; D011518:Proto-Oncogene Proteins; D013449:Sulfonamides; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D019098:Telomerase; C012655:nimesulide