Effects of p53 or p27 overexpression on cyclooxygenase-2 gene expression in head and neck squamous cell carcinoma cell lines.
BACKGROUND
Although cyclooxygenase-2 (COX-2) has been suggested to play an important role in carcinogenesis, the effects of tumor suppressors on COX-2 gene expression and the combined antitumor effects of tumor suppressors and COX-2 inhibitors have rarely been investigated.


METHODS
The effects of p53 or p27 gene transfer on COX-2 expression by adenoviral vector and the combined effects of p53 or p27 gene transfer and COX-2 inhibitor exposure on the proliferation of cancer cells were investigated in head and neck squamous cell carcinoma (HNSCC) cell lines.


RESULTS
Overexpression of p53 markedly downregulated the transcription of COX-2, but the overexpression of p27 did not affect COX-2 levels in HNSCC cell lines. The combined antitumor effects of p53 or p27 gene transfer and of a COX-2 inhibitor (NS 398) were mainly at least additive in terms of the inhibition of cell proliferation and cell cycle arrest and additive in terms of apoptotic induction.


CONCLUSIONS
These results suggest that the overexpression of p53 could exert antitumor effects, at least in part, through the suppression of COX-2 gene expression, whereas growth suppression by the overexpression of p27 probably occurs by mechanisms other than the downregulation of COX-2 expression. In addition, the administration of COX-2 inhibitors, as an adjunct to p53 or p27 gene therapy, could offer a new strategy of cancer treatment and prevention.
Lee
Dong Wook
DW
Department of Otorhinolaryngology-Head and Neck Surgery and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea.
Park
Seok-Woo
SW
Park
Soo-Yeun
SY
Heo
Dae-Seog
DS
Kim
Kwang Hyun
KH
Sung
Myung-Whun
MW
D000704:Analysis of Variance; D017209:Apoptosis; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000502:physiology; D016158:Genes, p53 / Q000502:physiology*; D006258:Head and Neck Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D018797:Cell Cycle Proteins; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases