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.
Department of Otolaryngology, Head and Neck Surgical Oncology, Princess Margaret Hospital, Toronto, Ontario.
Antti A
AA
Mäkitie
Monica
M
Chau
Steve
S
Lim
Mary-Anne
MA
Viani
Ralph
R
Gilbert
Megan S
MS
Lim
Richard C K
RC
Jordan
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