The Cyclooxygenase-2 Inhibitor Nimesulide, a Nonsteroidal Analgesic, Decreases the Effect of Radiation Therapy in Head-and-Neck Cancer Cells
Department of Cranio-, Maxillofacial and Oral Surgery, Medical University of Vienna, Vienna, Austria. Strahlentherapie und Onkologie
(Impact Factor: 2.91).
06/2009; 185(5):310-7. DOI: 10.1007/s00066-009-1929-4
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.
Available from: Marc F Diederich
- "However, combination of COX-2 inhibitors with radiation therapy can also lead to a reduction of efficiency of the radiotherapy. In one report, it has been shown that the selective COX-2 inhibitor nimesulide decreased radiation efficiency of two head-and-neck cancer cells lines (SCC9 and SCC25) which are COX-2 positive . This suggests that the sensitization of tumor cells to radiation might be strongly dependent on tumor cell type. "
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ABSTRACT: It is well admitted that the link between chronic inflammation and cancer involves cytokines and mediators of inflammatory pathways, which act during the different steps of tumorigenesis. The cyclooxygenases (COXs) are a family of enzymes, which catalyze the rate-limiting step of prostaglandin biosynthesis. This family contains three members: ubiquitously expressed COX-1, which is involved in homeostasis; the inducible COX-2 isoform, which is upregulated during both inflammation and cancer; and COX-3, expressed in brain and spinal cord, whose functions remain to be elucidated. COX-2 was described to modulate cell proliferation and apoptosis mainly in solid tumors, that is, colorectal, breast, and prostate cancers, and, more recently, in hematological malignancies. These findings prompt us to analyze here the effects of a combination of COX-2 inhibitors together with different clinically used therapeutic strategies in order to further improve the efficiency of future anticancer treatments. COX-2 modulation is a promising field investigated by many research groups.
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The aim of the study was to explore the effects of the same target (si-10) on lung cancer cells with different expression levels of cyclooxygenase-2 (COX-2) protein by RNAi and malignant proliferation of these cells.
COX-2 was selected as the target and one siRNA expression vector with the best effect was selected and thought as the subject from three COX-2 siRNA expression vectors with human U6 promoter. The siRNA expression vector (psi-10) and the vacant vector (pEGFP) were transfected into these cells with different COX-2 expression states (801D, A549 and LTEP-A2) with lipofectamine respectively and the transfected cell strains were constructed. The change of COX-2 expression levels was examined by Western blot and RT-PCR. The effects on the proliferation of lung cancer cells were studied by cell growth curve and clonogenic assay.
The siRNA and U6 promoter were validated by PCR, restriction endonucleases identification and DNA sequencing and BLAST alignment and cloned into the pEGFP vector. The cell strains transfected that 801D was used as maternal line were named as 801D-p and 801D-10 respectively. The cell strains transfected that A549 was used as maternal line were named as A549-p and A549-10 respectively. The cell strains transfected that LTEP-A2 was used as maternal line were named as LTEP-A2-p and LTEP-A2-10 respectively. These cells transfected pEGFP (801D-p, A549-p and LTEP-A2-p) had the expression of GFP and 801D-10, A549-10 and LTEP-A2-10 cells had not in 24, 48 and 72 hours after transfected. The results of RT-PCR and Western blot showed the siRNA expression vector produced marked effects in two cells (A549 and LTEP-A2) expressing COX-2 and the expression of COX-2 was inhibited. But the inhibited effects were different and the expression of COX-2 was more inhibited obviously in LTEP-A2 cells than in A549 cells though the expression of COX-2 was also inhibited obviously in A549 cells. In contract to their maternal line, the levels of COX-2 mRNA of LTEP-A2-10 and A549-10 cells reduced 64.2% and 61.2% respectively; the levels of COX-2 protein reduced 60.2% and 56.2% respectively. But the levels of COX-2 mRNA and protein had not change in 801D cells not expressing COX-2. The results of cell growth curve and clonogenic assay showed the growth of LTEP-A2-10 cells slowed and the clonal formation rate reduced and the size of the colonies became small; the growth of A549-10 cells showed slow and more obviously in the cell growth curve especially. But the growth of 801D-10 cells had not obvious change.
The si-10 target of COX-2 has different inhibition effects on lung cancer cells with different COX-2 expression levels and the different inhibition effects have different effects on cells malignant proliferation.
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ABSTRACT: Betulinic acid, a pentacyclic triterpene, is a new cytotoxic compound active on melanoma, neuroblastoma, glioblastoma and head and neck squamous cell carcinoma (HNSCC) cells. In combination with irradiation it has been shown to have an additive effect on growth inhibition in melanoma cells. In this study, the radiosensitizing effect of betulinic acid on sequential irradiation was investigated in HNSCC cell lines.
Two HNSCC cell lines, SCC9 and SCC25, were treated with increasing doses of betulinic acid and sequentially irradiated with a single boost of 4 Gy from a conventional radiation source. The cells were counted, the surviving fraction was determined, and colony-forming assays were performed.
It could be shown that betulinic acid alone inhibits cell survival, affects cell survival additively in combination with irradiation and decreases clonogenic survival in both cell lines when applied alone.
Betulinic acid could be a promising treatment agent in radioresistant head and neck cancer. A combination of betulinic acid with radiotherapy seems to be beneficial.
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