ABSTRACT
Asthma is a chronic airway inflammatory disease, and airway remodeling is one of its typical pathological features.Airway remodeling can result in hyperactivity, irreversible airflow limitation, and even decreased lung function.Studies have shown that the Wnt/β-catenin signaling pathway plays an important role in post-injury repair of the lung.Abnormal activation of the Wnt/β-catenin signaling pathway leads to airway remodeling in asthma.This article will review the progress of Wnt/β-catenin signaling pathway and asthma-related airway remodeling, and explore its possible therapeutic targets in asthma.
ABSTRACT
<p><b>OBJECTIVE</b>To correlate delayed rectifier K(+) channel to cyclooxygenase-2 (COX-2) in onco genesis of human gastric cancer cell.</p><p><b>METHODS</b>Human COX-2 encoding gene was cloned with RT-PCR strategy and its antisense recombinant eukaryotic expression vector was constructed. COX-2 highly expressed human gastric cancer cell line SGC7901 was stably transfected with the antisense vector. The whole-cell recording technique of perforated patch clamp was employed to observe the change of delayed rectifier K(+) current (I(k)) of SGC7901 after gene transfer or treatment with COX-2 inhibitor indomethacin. MTT was also performed to determine the effect of delayed rectifier K(+) channel inhibitors on cell growth.</p><p><b>RESULTS</b>Stably transfected cell (7901-AS) was obtained and a down-regulated expression of COX-2 protein and mRNA in the cell was achieved. Patch clamp recording showed that both SGC7901 and 7901-AS cells had a typical delayed rectifier K(+) current. However, I(k) was significantly lower (P < 0.01) in transfected cell or cell treated with indomethacin at each test potential. The altered I(k) could be entirely recovered after drug removal from the cells. K(+) channel blockers tetraethylammonium (TEA) and 4-aminopyridine (4-AP) could retard the growth of SGC7901 and the transfected cell in a dose-dependent manner.</p><p><b>CONCLUSION</b>Delayed rectifier K(+) channel, existing in human gastric cancer cell line SGC7901, is related to the growth of the cell. The highly expressed COX-2 may affect the biological behavior of gastric cancer cell by regulating this ion channel.</p>
Subject(s)
Humans , Cell Division , Physiology , Cyclooxygenase 2 , Delayed Rectifier Potassium Channels , Isoenzymes , Metabolism , Membrane Proteins , Potassium Channels , Metabolism , Potassium Channels, Voltage-Gated , Prostaglandin-Endoperoxide Synthases , Metabolism , Stomach Neoplasms , Metabolism , Tumor Cells, CulturedABSTRACT
Objective To compare the effect of seven commonly used nonsteroidal anti inflammatory drugs (NSAIDs) on proliferation, apoptosis, and neoplasmagenesis of gastric cancer cells in vivo. Methods Gastric cancer cell lines were treated with NSAIDs (aspirin 0-400 ?mol/L, indomethacin 0-25 ?mol/L, and ibuprofen, naproxen, sulindac, nimesulide, celecoxib 0-200 ?mol/L, respectively). Proliferation of the cells was detected by using MTT assay. Apoptosis of cells was measured by using fluorescence activated cell sorter (FACS). Nude mice bearing gastric cancer xenografts were administrated with NSAIDs (indomethacin 3 mg/kg, sulindac 8 mg/kg, nimesulide 6 mg/kg, celecoxib 15 mg/kg) for 30 days, and then the weight of implanted tumors was measured. Results There was a dose dependent inhibition of cell proliferation by majority of NSAIDs used, celecoxib the most, except for ibuprofen and naproxen. In nude mice, NSAIDs also showed a suppressive effect on tumor growth with inhibitory rate of celecoxib as (93.8?0.97)%, nimesulide (93.1?1.78)%, indomethacin (89.9?5.61)% and sulindac (89.3 ? 2.07)%. Once incubated with celecoxib and indomethacin, the gastric cancer cells went to apoptosis with an increase in percentage of apoptotic cells up to 30.4% and 23.9%, respectively. Conclusions Many NSAIDs, celecoxib in particular, appeared to be suppressive to gastric cancer cells with exception for ibuprofen and naproxen. Induction of apoptosis might be one of the mechanisms that NSAIDs inhibit gastric cancer.
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Objective To investigate the significance of expression of peroxisome proliferator activated receptor ?(PPAR?) and retinoid X receptor ?(RXR?) in chronic gastritis, gastric mucosal dysplasia and gastric carcinoma and to identify the correlation between PPAR? and RXR?. Methods Avidin biotin peroxidase complex immunohistochemical methods were adopted to examine the expression of PPAR? and RXR? in 53 patients with gastric carcinoma, and 18 with gastric mucosal dysplasia, 31 with chronic non atrophic gastritis and 30 with chronic atrophic gastritis were served as controls. Results The positive rates of PPAR? and RXR? were 41.5% and 54.7% in gastric carcinoma respectively, 27.8% and 38.9% in gastric mucosal dysplasia, 10.0% and 20.0% in chronic atrophic gastritis, 6.5% and 16.1% in chronic non atrophic gastritis. From chronic non atrophic gastritis, chronic atrophic gastritis to gastric carcinoma, expressions of PPAR? and RXR? showed an ascending tendency. Compared with those in chronic gastritis, expressions of PPAR? and RXR? in gastric mucosal dysplasia and gastric carcinoma were significantly enhanced ( P0.05). There was a significant correlation between expressions of PPAR? and RXR? in gastric carcinoma ( r =0.54). Conclusion PPAR? and RXR? protein overexpression is a relatively early event in gastric carcinogenesis, and it may play both an independent and synergetic role in progression of gastric carcionma.
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The aims of this study were to compare the inhibitory effect of nimesulide and indomethacin on gastric cancer cells, to investigate the effect of nimesulide on SGC7901 and 7901-AS, and to evaluate its probable mechanism. After incubated with nimesulide (0～200?mol/L) or indomethacin (0～25?mol/L), the proliferation of gastric cancer cells was measured by MTT assay. The cell cycle of SGC7901, 7901-P, 7901-AS was respectively observed after being incubated with nimesulide and vehicle control, by using fluorescence activated cell sorter (FACS). Ultramicrostructure of gastric cancer cells (SGC7901,7901-AS,SGC7901+nimesulide) was observed by electronmicroscopy. The results showed that by MTT assay nimesulide, as indomethacin, had dose-dependent inhibitory effects on proliferation of gastric cancer cells. Compared to the inhibitory effect of nimesulide on SGC7901, it was less on 7901-AS (P