Selective inhibition of cyclooxygenase 2 induces p27kip1 and skp2 in oral squamous cell carcinoma.
It has been shown that inhibition of cyclooxygenase 2 (COX-2) may cause growth arrest and reduced tumour formation in some human cancers; however, the mechanism is not fully known. In this study, we used an oral squamous cell carcinoma cell line to study growth inhibition and changes in critical cell cycle-regulating proteins induced by the selective COX-2 inhibitor celecoxib. Using cell viability assay, we established the optimal in vitro inhibitory dose of celecoxib and showed that inhibition of COX-2 markedly induces the expression of p27kip1, p21, waf1, and the F-box protein skp2. These results add new experimental data to our knowledge of the mechanism of cyclooxygenases on neoplastic cells.
Mäkitie
Antti A
AA
Department of Otolaryngology, Head and Neck Surgical Oncology, Princess Margaret Hospital, Toronto, Ontario.
Chau
Monica
M
Lim
Steve
S
Viani
Mary-Anne
MA
Gilbert
Ralph
R
Lim
Megan S
MS
Jordan
Richard C K
RC
D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D000068579:Celecoxib; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology / Q000627:therapeutic use; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008565:Membrane Proteins; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D044786:S-Phase Kinase-Associated Proteins / Q000096:biosynthesis*; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*
D018797:Cell Cycle Proteins; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011720:Pyrazoles; D044786:S-Phase Kinase-Associated Proteins; D013449:Sulfonamides; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib; D007213:Indomethacin