The cyclooxygenase-2 inhibitor nimesulide, a nonsteroidal analgesic, decreases the effect of radiation therapy in head-and-neck cancer cells.
ABSTRACT No data are available on the effects of the cyclooxygenase-2 (COX-2) inhibitor nimesulide in combination with irradiation on the survival of head-and-neck carcinoma cells.
Two head-and-neck carcinoma cell lines (SCC9 and SCC25) were treated with nimesulide (50-600 microM) and irradiated concomitantly or sequentially. Early effects on cell survival were investigated by counting cell numbers, long-term effects by colony-forming assays. Cell-cycle effects were analyzed 24-72 h after treatment with nimesulide by flow cytometry.
Unexpectedly, nimesulide solely inhibited cell proliferation without affecting colony-forming ability. In addition, no evidence for a radiosensitizing effect of nimesulide in short-term assays was seen. Nimesulide alone had no effect on clonogenic survival alone or in combination with radiation.
Nimesulide differentially affects cell proliferation and clonogenic survival and may decrease the efficacy of radiotherapy. Short-term assays to assess tumor growth may not correctly predict the clinically relevant long-term effect of COX-2 inhibitors.
- Strahlentherapie und Onkologie 03/1994; 170(2):116-7. · 4.16 Impact Factor
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ABSTRACT: Cyclooxygenase (COX) catalyzes the conversion of arachidonic acid to prostaglandin H2. The inducible isoform, COX-2, promotes colorectal tumorigenesis, and nonsteroidal anti-inflammatory drugs (NSAIDs) that selectively inhibit this isoform are chemopreventive in murine models of intestinal tumorigenesis. To establish a mechanism for their chemopreventive properties, we examined the effect of a COX-2-selective inhibitor, NS-398, on two colorectal carcinoma cell lines: HT29, which was found to express COX-2 protein constitutively; and S/KS, which did not express detectable levels of COX-2 protein. NS-398 had a dose-dependent antiproliferative effect on each cell line (IC50, 82.0 +/- 10.1 microM for HT29 and 78.6 +/- 11.1 microM for S/KS), and this was due to the induction of apoptosis. Cell cycle parameters were unaffected by NS-398 treatment. The ability of NS-398 to induce apoptosis provides a potential mechanism by which COX-2-selective inhibitors are chemopreventive and also indicates their potential as chemotherapeutic agents for colorectal cancer. That this effect was independent of COX-2 protein expression suggests that COX-2-selective NSAIDs may, like nonselective NSAIDs, be antineoplastic in the absence of COX-2.Clinical Cancer Research 11/1997; 3(10):1679-83. · 7.84 Impact Factor
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ABSTRACT: Results of preclinical studies suggesting that the efficacy of molecular therapies is enhanced when they are combined with radiation have generated a surge of clinical trials combining these modalities. We reviewed the literature to identify the rationale and experimental foundation supporting the use of cyclooxygenase-2 (COX-2) inhibitors with standard radiotherapy regimens in current clinical trials. Radiation affects the ability of cells to divide and proliferate and induces the expression of genes involved in signaling pathways that promote cell survival or trigger cell death. Future advances in radiotherapy will hinge on understanding mechanisms by which radiation-induced transcription of genes governs cell death and survival, the selective control of this process, and the optimal approaches to combining this knowledge with existing therapeutic modalities. COX-2 is expressed in all stages of cancer, and in several cancers its overexpression is associated with poor prognosis. Evidence from clinical and preclinical studies indicates that COX-2-derived prostaglandins participate in carcinogenesis, inflammation, immune response suppression, apoptosis inhibition, angiogenesis, and tumor cell invasion and metastasis. Clinical trial results have demonstrated that selective inhibition of COX-2 can alter the development and the progression of cancer. In animal models, selective inhibition of COX-2 activity is associated with the enhanced radiation sensitivity of tumors without appreciably increasing the effects of radiation on normal tissue, and preclinical evidence suggests that the principal mechanism of radiation potentiation through selective COX-2 inhibition is the direct increase in cellular radiation sensitivity and the direct inhibition of tumor neovascularization. Results of current early-phase studies of non-small-cell lung, esophageal, cervical, and brain cancers will determine whether therapies that combine COX-2 inhibitors and radiation will enter randomized clinical trials.CancerSpectrum Knowledge Environment 11/2003; 95(19):1440-52. · 14.07 Impact Factor