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.
"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. "
[Show abstract][Hide abstract] 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.
International Journal of Cell Biology 03/2010; 2010(1687-8876):215158. DOI:10.1155/2010/215158
[Show abstract][Hide abstract] ABSTRACT: ObjectiveThe 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.
MethodsCOX-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.
ResultsThe 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.
ConclusionThe 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.
Key wordscyclooxygenase-2 (COX-2)-lung cancer cells-RNAi-malignant proliferation
The Chinese-German Journal of Clinical Oncology 03/2010; 9(3):125-132. DOI:10.1007/s10330-009-0144-1
[Show abstract][Hide abstract] 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.
Strahlentherapie und Onkologie 02/2010; 186(3):143-8. DOI:10.1007/s00066-010-2069-6 · 2.91 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.