Celecoxib ; Cell Proliferation ; drug effects ; Drug Resistance, Multiple ; Humans ; Interferon-alpha ; pharmacology ; K562 Cells ; Pyrazoles ; pharmacology ; Sulfonamides ; pharmacology

The aim of this study was to investigate the effects of Celecoxib on the proliferation, apoptosis, cell cycle and CD117 expression of K562 cells, and to explore its synergistic effect with IFN-alpha. K562 cells were treated with IFN-alpha, Celecoxib and combination of Celecoxib with IFN-alpha at different concentrations. The inhibitory effect of Celecoxib and IFN-alpha on cell proliferation was detected with MTT assay, the cell apoptosis, cell cycle and CD117 expression were determined by morphology observation and flow cytometry. The results showed that the Celecoxib inhibited proliferation of K562 cells in concentration-dependent manner (r=-0.91). After culture of K562 cells for 72 hours, the rates of K562 cell proliferation in control group, IFN-alpha group, Celecoxib group and IFN-alpha-combined Celecoxib group were (96.1+/-0.5)%, (90.2+/-0.4)%, (57.2+/-0.9)% and (21.9+/-0.3)% respectively. The cell apoptosis rates in 4 groups were (5.5+/-0.8)%, (6.3+/-0.6)%, (26.4+/-3.9)% and (57.3+/-4.5)% respectively. The CD117 expression rates in 4 groups were 54.7%, 10.5%, 36.3% and 7.3% respectively. Combination of Celecoxib with IFN-alpha might block K562 cells in G0/G1 phase. In conclusion, Celecoxib and IFN-alpha both may inhibit K562 cell proliferation, induce apoptosis, reduce CD117 expression and produce G0/G1 phase block to various degree and the two drugs have a synergistic effect.
Apoptosis ; drug effects ; Celecoxib ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Humans ; Interferon-alpha ; pharmacology ; K562 Cells ; Proto-Oncogene Proteins c-kit ; metabolism ; Pyrazoles ; pharmacology ; Sulfonamides ; pharmacology

OBJECTIVETo investigate the role of COX-2 inhibitor celecoxib in inhibiting the migration of human tongue squamous cell carcinoma Tca8113 cells.

METHODSThe effects of celecoxib on Tca8113 cell migration were tested using scrape motility assay, cell-matrix adhesion assay and Boyden chamber motility assay.

RESULTSFollowing a 24-hour incubation with 10 and 20 micromol/L celecoxib, the migration of Tca8113 cells was significantly decreased (Plt;0.05). Celecoxib treatment for 24 h also resulted in significantly decreased adhesion of Tca8113 cells on Fn-coated surface in a dose-dependent manner.

CONCLUSIONCOX-2 inhibitor celecoxib can inhibit Tca8113 cell migration, the mechanism of which awaits further investigation.

Carcinoma, Squamous Cell ; pathology ; Celecoxib ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cyclooxygenase 2 Inhibitors ; pharmacology ; Humans ; Pyrazoles ; pharmacology ; Sulfonamides ; pharmacology ; Tongue Neoplasms ; pathology

OBJECTIVE: To detect the effect of Celecoxib on the proliferation and apoptosis of human nasopharyngeal carcinoma cell line CNE-2. METHOD: The growth inhibition rate of CNE-2 by Celecoxib was evaluated with MTT method. Apoptosis related morphology changes were observed with transmission electron microscopy (TEM). The cell cycle and apoptosis were measured with flow cytometric method (FCM). Apoptotic index (AI) was counted by the TDT-mediated dUTP-biotin nick end-labeling (TUNEL) assay. RESULT: The growth of CNE-2 cell was inhibited by celecoxib in a dose-and time-dependent manner. Apoptosis with nuclear chromatin condensation, cell shrinkage, periplasm loss and the formation of apoptotic bodies was observed with TEM. Apoptotic rates of CNE-2 cells treated with 80 and 100 micromol/L celecoxib were (10.47+/-0.18)% and (20.17+/-0.55)% respectively, significantly higher than those of the control group (1.57+/-0.27)% with FCM. The percentage of G0/G1 phase cells increased, whereas the S and G2/M phases cells decreased in a dose-dependent manner after the treatment. TUNEL assay showed that the apoptosis ratio (AI) of CNE-2 treated with Celecoxib was higher than control group (P<0.01). CONCLUSION Celecoxib can inhibit the growth of human nasopharyngeal carcinoma cell line CNE-2 and induce the cell apoptosis, which may be related to blocking the cell cycle progress of CNE-2 cells.
Apoptosis ; drug effects ; Celecoxib ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclooxygenase 2 Inhibitors ; pharmacology ; Humans ; Nasopharyngeal Neoplasms ; pathology ; Pyrazoles ; pharmacology ; Sulfonamides ; pharmacology

This study was conducted to evaluate the growth and NAG-1 gene expression effected by Non-steroidal anti-inflammatory drug (NSAID) on colon cancer cell lines in vitro. The proliferation of colon cancer cells were determined by MTT assay and COX-2 protein expression were detected by Western blot. Total RNA was isolated from three kinds of colon cancer cell lines; the expressions of NAG-1 mRNA in the cells treated with or without NSAIDs were assessed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay. Celecoxib, meloxicam and aspirin were able to inhibit the growth of HT-29, SW480 and LS174-T cells in dose-dependent manner. COX-2 protein expressed in HT-29 and LS174-T, but not in SW480 cells. All of colon cancer cells expressed NAG-1 gene and the level of LS174-T was lower than that of the other two cell lines. NAG-1 expression was increased by treatment with some NSAIDs in all three kinds of colon cancer cells. NSAIDs were able to potentially inhibit the growth of colon cell lines. Induction of NAG-1 gene expression by NSAID was not consistent with COX-2 expression.
Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Antineoplastic Agents ; pharmacology ; Aspirin ; pharmacology ; Celecoxib ; Cell Proliferation ; drug effects ; Cyclooxygenase 2 ; metabolism ; Gene Expression Regulation, Neoplastic ; HT29 Cells ; Humans ; Neoplasm Proteins ; metabolism ; Pyrazoles ; pharmacology ; RNA, Messenger ; metabolism ; Sulfonamides ; pharmacology ; Thiazines ; pharmacology ; Thiazoles ; pharmacology

OBJECTIVETo study the effect of cyclooxygenase -2 selective inhibitor celecoxib on the expression of major vault protein ( MVP) in the brain of rats with status epilepticus and its possible roles in the treatment of refractory epilepsy.

METHODSSixty adult male Sprague-Dawley rats were randomly assigned to blank control (n=16), epilepsy model (n=22) and celecoxib treatment groups (n=22). After the status epilepticus was induced in rats by injecting lithium and pilocarpine, each group had 16 rats enrolled as subjects. Immunohistochemical method and Western blot method were used to detect the expression of MVP in the frontal cortex and hippocampus.

RESULTSThe expression of MVP was significantly higher in the epilepsy model group than in the control group (P<0.01). The expression of MVP in the celecoxib treatment group was significantly decreased compared with the epilepsy model group, but it was still higher than in the control group (P<0.01).

CONCLUSIONSCelecoxib could decrease the expression of MVP in brain tissue of rats with status epilepticus, suggesting that it is promising for the treatment of intractable epilepsy.

Animals ; Blotting, Western ; Brain ; metabolism ; Celecoxib ; pharmacology ; therapeutic use ; Cyclooxygenase 2 Inhibitors ; pharmacology ; Immunohistochemistry ; Male ; Rats ; Rats, Sprague-Dawley ; Status Epilepticus ; drug therapy ; metabolism ; Vault Ribonucleoprotein Particles ; analysis

OBJECTIVETo explore the antagonizing effect of celecoxib against the cytotoxicity of carboplatin in human esophageal cancer cells.

METHODSThe cell viability of cisplatin-resistant cell line EC109/CDDP and its parental cell line EC109 exposed to carboplatin alone or carboplatin plus celecoxib was determined by MTT assay. The expression of CTR1, caspase-3 activation and PARP cleavage in the exposed cells were examined by Western blotting. Caspase-3 activity and cell apoptosis after the exposure were detected with Caspase-3/7 assay and flow cytometry, respectively. The effect of celecoxib on carboplatin accumulation in the cells was measured using inductively coupled plasma mass spectrometry (ICP-MS).

RESULTSCelecoxib treatment significantly increased the IC50 of carboplatin, suppressed carboplatin-induced caspase-3 and PARP cleavage and caspase-3 activity in EC109 and EC109/CDDP cells. Celecoxib also inhibited carboplatin-induced apoptosis and suppressed intracellular carboplatin accumulation in both cell lines. A combined exposure to celecoxib and carboplatin did not cause significant changes in the protein expression of CTR1.

CONCLUSIONCelecoxib antagonizes the cytotoxic effect of carboplatin and inhibits carboplatin-induced apoptosis in human esophageal cancer cells by reducing intracellular carboplatin accumulation.

Apoptosis ; Blotting, Western ; Carboplatin ; antagonists & inhibitors ; Caspase 3 ; metabolism ; Celecoxib ; Cell Line, Tumor ; drug effects ; Cell Survival ; Drug Interactions ; Esophageal Neoplasms ; metabolism ; pathology ; Humans ; Pyrazoles ; pharmacology ; Sulfonamides ; pharmacology

OBJECTIVETo study the effects of celecoxib on the cell proliferation and expression of vascular endothelial growth factor (VEGF) in human nasopharyngeal carcinoma line.

METHODS3-[ 4,5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) test was used to investigate the cell proliferation. Flow cytometry (FCM) was used to analyze the cell cycle arrest. Immunocytochemistry technique was to observe the expression of VEGF.

RESULTSCelecoxib inhibited the growth of nasopharyngeal carcinoma line, the cell number of G0/G1 phase increased from 62.13% to 91.35%, and the cell number of G2/M and S phase decreased from 21.59% to 3.56% and from 16.28% to 5.01%, respectively, cell cycle progression was arrested at G1/S phase. Celecoxib decreased the positive expression of VEGF in HNE-1 cells.

CONCLUSIONSCelecoxib inhibited the proliferation of nasopharyngeal carcinoma significantly and the expression of VEGF.

Celecoxib ; Cell Line, Tumor ; drug effects ; metabolism ; Cell Proliferation ; drug effects ; Humans ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Pyrazoles ; pharmacology ; Sulfonamides ; pharmacology ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVE: Drug-resistance and metastasis are major reasons for the high mortality of ovarian cancer (OC) patients. Cyclooxygenase-2 (COX-2) plays a critical role in OC development. This study was designed to evaluate the effects of COX-2 on migration and cisplatin (cis-dichloro diammine platinum, CDDP) resistance of OC cells and explore its related mechanisms. METHODS: Cell counting kit-8 (CCK-8) assay was used to detect the cytotoxicity effects of celecoxib (CXB) and CDDP on SKOV3 and ES2 cells. The effect of COX-2 on migration was evaluated via the healing test. Western blot and real-time quantitative polymerase chain reaction (qPCR) were used to analyze E-cadherin, vimentin, Snail, and Slug levels. RESULTS: COX-2 promoted drug-resistance and cell migration. CXB inhibited these effects. The combination of CDDP and CXB increased tumor cell sensitivity, reduced the amount of CDDP required, and shortened treatment administration time. COX-2 upregulation increased the expression of Snail and Slug, resulting in E-cadherin expression downregulation and vimentin upregulation. CONCLUSIONS COX-2 promotes cancer cell migration and CDDP resistance and may serve as a potential target for curing OC.
Celecoxib/pharmacology* ; Cell Line, Tumor ; Cell Movement ; Cisplatin/pharmacology* ; Cyclooxygenase 2/physiology* ; Drug Resistance, Neoplasm ; Epithelial-Mesenchymal Transition ; Female ; Humans ; Ovarian Neoplasms/pathology* ; Polymerase Chain Reaction

BACKGROUNDThe effect of selective and non-selective cyclooxygenase (COX) inhibitors on tendon healing was variable. The purpose of the study was to evaluate the influence of non-selective COX inhibitor, ibuprofen and flurbiprofen axetil and selective COX-2 inhibitor, celecoxib on the tendon healing process in a rabbit model.

METHODSNinety-six New Zealand rabbits were used as rotator cuff repair models. After surgery, they were divided randomly into four groups: ibuprofen (10 mg·kg-1·d-1), celecoxib (8 mg·kg-1·d-1), flurbiprofen axetil (2 mg·kg-1·d-1), and control group (blank group). All drugs were provided for 7 days. Rabbits in each group were sacrificed at 3, 6, and 12 weeks after tendon repair. Tendon biomechanical load failure tests were performed. The percentage of type I collagen on the bone tendon insertion was calculated by Picric acid Sirius red staining and image analysis. All data were compared among the four groups at the same time point. All data in each group were also compared across the different time points. Qualitative histological evaluation of the bone tendon insertion was also performed among groups.

RESULTSThe load to failure increased significantly with time in each group. There were significantly lower failure loads in the celecoxib group than in the control group at 3 weeks (0.533 vs. 0.700, P = 0.002), 6 weeks (0.607 vs. 0.763, P = 0.01), and 12 weeks (0.660 vs. 0.803, P = 0.002), and significantly lower percentage of type I collagen at 3 weeks (11.5% vs. 27.6%, P = 0.001), 6 weeks (40.5% vs. 66.3%, P = 0.005), and 12 weeks (59.5% vs. 86.3%, P = 0.001). Flurbiprofen axetil showed significant differences at 3 weeks (failure load: 0.600 vs. 0.700, P = 0.024; percentage of type I collagen: 15.6% vs. 27.6%, P = 0.001), but no significant differences at 6 and 12 weeks comparing with control group, whereas the ibuprofen groups did not show any significant difference at each time point.

CONCLUSIONSNonsteroidal anti-inflammatory drugs can delay tendon healing in the early stage after rotator cuff repair. Compared with nonselective COX inhibitors, selective COX-2 inhibitors significantly impact tendon healing.

Animals ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Biomechanical Phenomena ; Celecoxib ; pharmacology ; Cyclooxygenase 2 Inhibitors ; pharmacology ; Flurbiprofen ; pharmacology ; Ibuprofen ; pharmacology ; Male ; Rabbits ; Rotator Cuff ; drug effects ; pathology ; Tendon Injuries ; drug therapy ; Wound Healing ; drug effects