Celecoxib is a selective inhibitor of cyclooxygenase-2 (COX-2) that is a critical factor in carcinogenesis, but precise mechanism of its action remains to be elucidated. Here we evaluated the inhibitory effect of celecoxib on cell growth of human oral squamous cell carcinoma (OSCC) YD-10B, which was established to be used as in vitro OSCC model, and identified celecoxib-regulated protein by proteomics techniques. Celecoxib (IC50=37 micrometer) inhibited the growth of YD-10B cells with the decrease of COX-2 protein expression. Its inhibition could be linked in the arrest of G1 phase with increased levels of p(27)protein, a specific CDK inhibitor. Using proteomics, the 10- to 20-fold increase of heterogeneous nuclear ribonuclear protein C (hnRNP C), which has been suggested to be related with the translation of p(27)mRNA, was observed in celecoxib-treated YD-10B cells. In summary, celecoxib has a potential to induce the protein expression of hnRNP C and its increase subsequently induce the translation of p(27)mRNA, which trigger the inhibition of cell growth via p(27)-regulated cell cycle arrest in YD-10B cells. In addition, YD-10B cells could be useful to study the pathological mechanism of OSCC.
Tumor Cells, Cultured ; Tongue Neoplasms/metabolism/pathology ; Sulfonamides/*pharmacology ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Pyrazoles/*pharmacology ; Proteomics/methods ; Male ; Immunoblotting ; Humans ; Heterogeneous-Nuclear Ribonucleoprotein Group C/analysis/*metabolism ; Electrophoresis, Gel, Two-Dimensional ; Cyclooxygenase Inhibitors/pharmacology ; Cyclooxygenase 2/metabolism ; Cyclin-Dependent Kinase Inhibitor p27/analysis/metabolism ; Cell Survival/drug effects ; Cell Proliferation/*drug effects ; Cell Line, Tumor ; Cell Cycle/drug effects ; Carcinoma, Squamous Cell/metabolism/pathology ; Aged ; Actins/metabolism