Nimesulide inhibits proliferation via induction of apoptosis and cell cycle arrest in human gastric adenocarcinoma cell line.
OBJECTIVE
To evaluate the potential role of Nimesulide, a selective COX-2 inhibitor, in proliferation and apoptosis of gastric adenocarcinoma cells SGC7901.


METHODS
Cell counts and MTT assay were used to quantify the influence of Nimesulide in the proliferation of SGC7901 cells. Transmission electron microscopy and flow cytometry were used to observe the induction of Nimesulide the apoptosis of SGC7901 cells and influence in the distribution of cell cycle. The expression of P27(kip1) protein was observed by immunocytochemical staining.


RESULTS
SGC-7901 Cells treated with Nimesulide at various concentrations exhibited a profound dose- and time-dependent reduction in the proliferation rate over the 72 h test period. The highest survival rate of the cells was 78.7 %, but the lowest being 22.7 %. Nimesulide induced apoptosis of the cells in a dose-dependent and non-linear manner and increased the proportion of cells in the G(0)/G(1) phase and decreased the proportion in the S and G(2)/M phase of the cell cycle. Meanwhile, Nimesulide could up-regulate the expression of P27(kip1) protein.


CONCLUSIONS
The induction of apoptosis and cell cycle arrest are both anti-proliferative responses that likely contribute to the antineoplastic action of nimesulide on SGC-7901 cells. The up-regulation of P27(kip1) gene may contribute to the accumulation of these cells in the G(0)/G(1) phase following treatment with Nimesulide. Selective COX-2 inhibitor may be a new channel of the chemoprevention and chemotherapy for gastric carcinoma.
Li
Jian-Ying
JY
Department of Gastroenterology, Affiliated Union Hospital, Fujian Medical University, Fuzhou 350001, China. jyli99@hotmail.com
Wang
Xiao-Zhong
XZ
Chen
Feng-Lin
FL
Yu
Jie-Ping
JP
Luo
He-Sheng
HS
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D013449:Sulfonamides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018797:Cell Cycle Proteins; D016861:Cyclooxygenase Inhibitors; D013449:Sulfonamides; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; C012655:nimesulide