Expression levels of Akt in nimesulide-treated squamous carcinoma cell lines of the head and neck.
Nimesulide, a selective cyclooxygenase-2 (COX-2) inhibitor, is known to induce apoptosis in various cell lines. So far, the molecular targets that account for this effect are unknown. Akt and extracellular-signal regulated kinase (ERK) are both important signaling molecules, which promote survival in different types of cancer, including head and neck cancer. The aim of our study was to describe the effect of treatment with nimesulide and ERK inhibitor PD 98059 on the expression patterns of Akt within the head and neck cancer cell lines SCC 9 and SCC 25. SCC 9 and SCC 25 cells were cultured in RPMI and treated with nimesulide and PD 98059. Protein expression levels were semi-quantified by Western blot analysis. Apoptosis was examined using the M30 antibody that binds to a caspase cleaved cytoskeletal protein for detection of early apoptosis in immunofluorescence studies. In both cell lines, nimesulide treatment induced apoptosis and resulted in a decrease of Akt expression. ERK inhibition had no effect on Akt expression, and combined application of both agents had the same effect as treatment with nimesulide alone. In conclusion, nimesulide induces apoptosis and promotes down-regulation of Akt-expression in squamous cell carcinoma cells, independently of ERK activity.
Vormittag
Laurenz
L
Department of Internal Medicine, Division of Oncology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Lamm
Wolfgang
W
Erovic
Boban M
BM
Czembirek
Cornelia
C
Kornek
Gabriela
G
Thurnher
Dietmar
D
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D013449:Sulfonamides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D011518:Proto-Oncogene Proteins; D013449:Sulfonamides; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C012655:nimesulide