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. Copyright 2004 Wiley Periodicals, Inc.
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. Copyright 2004 Wiley Periodicals, Inc.