Selective COX-2 Inhibitor (Meloxicam) and Tooth-Supporting Bone Quality. A Histomorphometric Study in Rats

Abstract The effects of the non-steroidal anti-inflammatory drugs (NSAIDs) on bone quantity and quality were investigated for years. However, there is lack of information on the impact of NSAIDs on the quality of tooth-supporting alveolar bone in absence of periodontal inflammation. Thus, the aim of this study was to evaluate histometrically the influence of a selective COX-2 NSAID (Meloxicam) on the inter-radicular bone mineral density in rats. Forty-nine adult male Wistar rats were randomly divided into four experimental groups: Subcutaneous injection of 0.9% sterile saline for 15 days (G1; n=12) and 45 days (G2; n=11); and subcutaneous injection of Meloxicam for 15 days (G3; n=13) and 45 days (G4; n=13). Mineral density was histometrically determined in the inter-radicular area of the 1st mandibular molars and data analysis performed by two-way ANOVA (a=5%). Results showed no interaction between time and treatment (p>0.05) and that meloxicam did not affect the alveolar bone density. In contrast, it was found that inter-radicular alveolar bone density increased with time (91.88±3.08% and 92.86±2.38% for groups 15 and 45 days, respectively) (p<0.05). Within the limits of this study, daily administration of a selective COX-2 inhibitor (Meloxicam) did not affect the quality of the inter-radicular alveolar bone in absence of periodontal infection.

Resumo Os efeitos dos fármacos anti-inflamatórios não esteroidais (AINEs) sobre a quantidade e qualidade óssea tem sido investigados ao longo dos anos.Entretanto, há falta de informação sobre o impacto dos AINEs na qualidade do osso alveolar de suporte na ausência de inflamação periodontal. Assim, o objetivo deste estudo foi avaliar, histometricamente, a influência de um AINE seletivo para COX-2 (Meloxicam) na densidade mineral óssea inter-radicular em ratos. Quarenta e nove ratos Wistar, machos e adultos foram divididos aleatoriamente em quatro grupos experimentais: injeções subcutâneas de 0,9% de solução salina estéril por 15 dias (G1, n=12) e 45 dias (G2, n=11); e injeções subcutâneas de Meloxicam por 15 (G3, n=13) e 45 dias (G4, n=13). A densidade mineral foi determinada histometricamente na área inter-radicular dos primeiros molares mandibulares e a análise dos dados realizada por meio de ANOVA (a=5%). Os resultados mostraram nenhuma interação entre tempo e tratamento (p>0,05) e que o meloxicam não afetou a densidade óssea alveolar. Em contraste, foi encontrado que a densidade óssea alveolar inter-radicular aumentou ao longo do tempo (91,88±3,08% e 92,86±2,38% para os grupos 15 e 45 dias, respectivamente) (p<0,05). Dentro dos limites deste estudo, a administração diária de um inibidor seletivo para COX-2 (Meloxicam) não afetou a qualidade do osso alveolar inter-radicular na ausência de infecção periodontal.

A Randomized, Multicenter, Phase III Trial to Evaluate the Efficacy and Safety of Polmacoxib Compared with Celecoxib and Placebo for Patients with Osteoarthritis

BACKGROUND: The aim of this study was to evaluate the safety and analgesic efficacy of polmacoxib 2 mg versus placebo in a superiority comparison or versus celecoxib 200 mg in a noninferiority comparison in patients with osteoarthritis (OA). METHODS: This study was a 6-week, phase III, randomized, double-blind, and parallel-group trial followed by an 18-week, single arm, open-label extension. Of the 441 patients with knee or hip OA screened, 362 were randomized; 324 completed 6 weeks of treatment and 220 completed the extension. Patients were randomized to receive oral polmacoxib 2 mg (n = 146), celecoxib 200 mg (n = 145), or placebo (n = 71) once daily for 6 weeks. During the extension, all participants received open-label polmacoxib 2 mg. The primary endpoint was the change in Western Ontario and McMaster Universities (WOMAC)-pain subscale score from baseline to week 6. Secondary endpoints included WOMAC-OA Index, OA subscales (pain, stiffness, and physical function) and Physician's and Subject's Global Assessments at weeks 3 and 6. Other outcome measures included adverse events (AEs), laboratory tests, vital signs, electrocardiograms, and physical examinations. RESULTS: After 6 weeks, the polmacoxib-placebo treatment difference was −2.5 (95% confidence interval [CI], −4.4 to −0.6; p = 0.011) and the polmacoxib-celecoxib treatment difference was 0.6 (CI, −0.9 to 2.2; p = 0.425). According to Physician's Global Assessments, more subjects were “much improved” at week 3 with polmacoxib than with celecoxib or placebo. Gastrointestinal and general disorder AEs occurred with a greater frequency with polmacoxib or celecoxib than with placebo. CONCLUSIONS: Polmacoxib 2 mg was relatively well tolerated and demonstrated efficacy superior to placebo and noninferior to celecoxib after 6 weeks of treatment in patients with OA. The results obtained during the 18-week trial extension with polmacoxib 2 mg were consistent with those observed during the 6-week treatment period, indicating that polmacoxib can be considered safe for long-term use based on this relatively small scale of study in a Korean population. More importantly, the results of this study showed that polmacoxib has the potential to be used as a pain relief drug with reduced gastrointestinal side effects compared to traditional nonsteroidal anti-inflammatory drugs for OA.

Use of Parecoxib on postoperative analgesia for the elderly patients undergoing colorectomy / 中华普通外科杂志

Objective To evaluate Parecoxi on postoperative analgesia for the elderly patients undering colorectomy.Methods 82 patients were randomly divided into group of 44 patients undergoing open surgery and 38 patients receiving laparoscopic colorectomy.22 patients in open surgery using Parecoxib sodium combined with PCA analgesic way were named as observation group,while the other 22 patients using placebo combined with PCA analgesic way named as control group.19 laparoscopic surgery patients using Parecoxib sodium analgesia were named as observation group,while the other 19 patients using Tramadol analgesia named as control group.Results In the absence of any differences of VAS pain score,in the open surgery group,the average dosage of Fentanyl in observation group was (0.45 ± 0.23) mg vs.(0.78 ± 0.16) mg in observation group (P ＜ 0.05).Parecoxib reduced the dosage of Fentanyl of PCA in the open surgery group.In laparoscopic group,at the time of postoperative 6,12,24,48,72 h,in the observation group patients resting pain scores were 5.01 ±0.36,4.44 ±0.37,4.02 ±0.46,3.35 ±0.52,2.54 ±0.23 respectively,while in the control group patients resting pain scores were 5.86 ± 0.45,5.03 ± 0.64,4.89 ± 0.75,3.94 ± 0.73,2.56 ± 0.41 respectively,(P ＜ 0.01).The postoperative gastrointestinal function recovery time was (3.1 ±0.7) d in observation group vs.(5.9 ±0.4) d in the control group (P ＜0.01).The incidence of postoperative nausea and vomiting,were lower in observation group,(P ＜ 0.01).Conclusion Parecoxib can be used for postoperative analgesia in elderly patients with colorectal cancer,reducing the dosage of opioids,and protecting the patient's immune function.

Celecoxib promots the apoptosis of acute monocytic leukemia THP-1 cell line / 肿瘤

Objective: To investigate the effects of cyclooxygenase-2 (COX-2) inhibitor celecoxib on the proliferation and apoptosis of acute myeloid leukemia cells. Methods: After acute monocytic leukemia cell line THP-1 treatment with different concentrations of celecoxib, the proliferation, apoptosis and cell cycle distribution of THP-1 cells were detected by MTS and FCM, respectively. The expressions of cleaved-caspase-3, cleaved poly ADP-ribose polymerase-1 (cleaved-PARP-1), inhibitor of nuclear factor kappa-B kinase β (IKKβ), phospho- IKKβ (p-IKKβ), seride-threonine protein kinase (Akt), phospho-Akt (p-Akt) and survivin proteins in THP-1 cells were detected after treatment with different concentrations of celecoxib. Results: Different concentrations of celecoxib inhibited the proliferation of THP-1 cells, induced the apoptosis of THP-1 cells, and arrested the cell cycles of THP-1 cells at G0/G1 phase (all P 6 μmol/L) were significantly upregulated (all P < 0.05). Conclusion: Celecoxib can inhibit the proliferation and induce the apoptosis of THP-1.This effect may be related to Akt/nuclear factor kappa B (NF-κB) signaling pathway and the expression of anti-apoptotic protein survivin.

Inhibitory effect of interferonα-1b and cyclooxygenase-2 inhibitor on renal cancer cell and xenografts in nude mouse / 局解手术学杂志

Objective To investigate the inhibitory effect on human ACHN cell line and its mice xenograft by using interferon α-1b combined with cyclooxygenase-2 inhibitor and the relevant mechanism in vitro and vivo experiment .Methods ACHN cell and the xenograft mice were devided into 4 groups(IFN-α1b,NS398,IFNα-1b+NS398 and control group).The inhibitory effects were tested by CCK8(Cell Counting Kit 8)assay after AHCN were treated for 24 h and 48 h.The expression of bcl-xl and COX-2 were detected by Western blot .The vol-ume of the xenografts of ACHN cell line and testing the expression of VEGF in xenografts were measured by immunohistochemistry assay .Re-sults Both IFNα-1b and NS398 exerted inhibitory effects on ACHN and this effects showed a rising trend with a increasing concentration of drugs.The combined group was more significant than monotherapy group (P<0.05).Western blot assay showed that IFNα-1b and NS398 downregulated the expression of bcl-xl and COX-2 in ACHN.The combined group was more significant than monotherapy group (P<0.05). The combined group has the greatest inhibitory effects on the xenografts of ACHN cell line compared with monotherapy group and control group(P<0.05).The expression of VEGF in tumor was obiviously inhibited in combined group compared with monotherapy group and con -trol group (P<0.05).Conclusion IFNα-1b combined with NS398 can inhibit the proliferation of ACHN and suppress the tumor growth .

Update on the molecular targeted therapy for cervical cancer / 中国癌症杂志

Cervical cancer is one of the most common and deadliest cancers in females worldwide. Despite the treatment methods of surgery, radiotherapy and chemotherapy are maturing, the prognosis of patients with recurrent, advanced or metastatic cervical cancer remains poor. Molecular targeted therapy provides new hope for these patients. This review focuses on the advances in agents targeting vascular endothelial growth factor pathway, epidermal growth factor receptor, mammalian target of rapamycin, histone deacetylases and cyclooxygenase-2 in cervical cancer.

Influence of Celecoxib on Radiosensization of Irradiation￣resistant Cell Line CNE￣2R ofNasopharyngeal Carcinoma / 医药导报

Objective To investigate the effect of COX￣2 inhibitor celecoxib on radiosensitity of irradiation￣resistant cell line CNE￣2R of nasopharyngeal carcinoma and the potential mechanism. Methods Via exposing to a series of X￣ray (2, 4, 6, 8 Gy, 3 times for each dose), radio￣resistant cell subline CNE￣2R was established from human nasopharyngeal carcinoma cell CNE￣2.Radiosensitivity was detected by clone formation assay.CNE￣2R and CNE￣2 cell lines were exposed to 25, 50, 75 μmol.L-1 celecoxib, respectively.Western blotting was used to detect the protein expression of COX￣2.Clone formation assay was performed to measure the survival fraction of CNE￣2 and CNE￣2R after radiotherapy alone or radiotherapy combined with 30 μmol.L-1 celecoxib treatment.Flow cytometry was used to measure influence of radiotherapy alone or radiotherapy combined with 30 μmol.L￣1celecoxib treatment on cell apoptosis.Number of residual γ￣H2AX foci was observed by immunofluorescence assay. Results The colony forming assay demonstrated that the values of SF2, D0 , Dq , and N of CNE￣2R cell subline [(0.81±0.05), (2.15±0.07) Gy, (2.94±0.08) Gy, (3.91±0.07), respectively] was significant higher than those of CNE￣2 cell line [(0.61±0.08), (1.47±0.06) Gy, (1. 68 ± 0. 10) Gy, (3. 13 ± 0. 05), respectively]. The expression of COX￣2 protein was significantly downregulated with increasing celecoxib concentration.Surviving fraction was decreased in both CNE￣2 and CNE￣2R cell lines after irradiation.After radiotherapy combined with celecoxib, apoptosis rates of CNE￣2 and CNE￣2R cell lines [(13.10±0.63)%, (5.30±0.75)%] were higher than those of the corresponding control groups [(4.90±0.71)%, (1.82±0.82)%].Celecoxib increased radiosensitivity in nasopharyngeal carcinoma CNE￣2R and CNE￣2 cell lines.The number of residual γ￣H2AX foci after irradiation was increased by celecoxib pretreatment.The difference was statistically significant (P<0.05). Conclusion Celecoxib can enhance radiosensitivity of radio￣resistant cell subline CNE￣2R of human nasopharyngeal carcinoma in vitro.

Cellular and molecular studies of the effects of a selective COX-2 inhibitor celecoxib in the cardiac cell line H9c2 and their correlation with death mechanisms

Cardiovascular disease is one of the leading causes of death worldwide, and evidence indicates a correlation between the inflammatory process and cardiac dysfunction. Selective inhibitors of cyclooxygenase-2 (COX-2) enzyme are not recommended for long-term use because of potentially severe side effects to the heart. Considering this and the frequent prescribing of commercial celecoxib, the present study analyzed cellular and molecular effects of 1 and 10 µM celecoxib in a cell culture model. After a 24-h incubation, celecoxib reduced cell viability in a dose-dependent manner as also demonstrated in MTT assays. Furthermore, reverse transcription-polymerase chain reaction analysis showed that the drug modulated the expression level of genes related to death pathways, and Western blot analyses demonstrated a modulatory effect of the drug on COX-2 protein levels in cardiac cells. In addition, the results demonstrated a downregulation of prostaglandin E2 production by the cardiac cells incubated with celecoxib, in a dose-specific manner. These results are consistent with the decrease in cell viability and the presence of necrotic processes shown by Fourier transform infrared analysis, suggesting a direct correlation of prostanoids in cellular homeostasis and survival.

Experimental antibacterial activity of selective cyclooxygenase antagonist.

Background: From the history of the development of pharmaceutical compounds it is evident that any drug may have the possibility of possessing diverse functions and thus may have useful activity in completely different fields of medicine and different studies showed that newer antimicrobials have revealed antimicrobial action involved in the management of diseases of non-infectious etiology. This study was done to determine in vitro antibacterial activity of selected selective cyclooxygenase-2 inhibitor. Methods: Twenty two strains of gram positive and gram negative bacteria, which were isolated from skin and urinary tract infected patient. These bacteria were being cultured on specific optimal growth media. The antibacterial activity of selective COX-2 (meloxicam, celecoxib, valdecoxib and nimesulide). Inhibitors determined by measuring zone of inhibition and minimal inhibitory concentration (MIC). Results: Results showed that MIC of celecoxib and meloxicam in μg/ml was ranged from 5-80μg/ml on selected bacteria compared with negative control distilled water (D.W) ,valdecoxib was 80-160μg/ml, while and nimesulide was ranged from 5-40 μg/ml .All the selected bacteria were showed sensitivity for all coxib used in this experimental study except Pseudomonas aeruginosa which showed resistant to meloxicam and valdecoxib, Klebsiella pneumoniae resist to nimesulide while Staphylococcus aureus was resist to valdecoxib. The smaller zone of inhibition showed by valdecoxib and celecoxib which was 3mm against Klebsiella pneumoniae, while the larger zone of inhibition showed by nimesulide which was 26mm against Escherichia coli. Conclusions: In conclusion selective cyclooxygenase (cox-2) inhibitor possesses antibacterial activity this is especially for nimesulide and little by valdecoxib. Escherichia coli are sensitive bacteria to all coxib. Consequently; coxib may be regarded as anti-inflammatory and antibacterial agent especially for urinary tract infection where Escherichia coli are the major causative organism.

The Effects of Preemptive Analgesia to Blood Transfusion in Total Knee Arthroplasty / 대한수혈학회지

BACKGROUND: Total knee arthroplasty (TKA) is associated with moderate to severe postoperative pain. In recent studies, preemptive analgesia was useful for control of postoperative pain in patients undergoing TKA. In particular, cyclooxygenase-2 inhibitor (celecoxib) is recommended for preemptive analgesia. As a large amount of blood is lost during TKA, blood transfusion is often required. In this study, we evaluated the difference of intraoperative blood loss, complications of operation, and hemodynamic change between the celecoxib group and the control group in TKA surgeries. METHODS: A total of 58 patients who underwent TKA from January 2013 to June 2013 in our hospital were evaluated through a retrospective study. Patients in the celecoxib group received 200 mg of oral celecoxib 1 to 2 hours before TKA. Those in the control group received no medication 1 to 2 hours before TKA. Preoperative and postoperative hemoglobin level, estimated blood loss, infused fluid volume, and intraoperative complications (nausea, vomiting) were assessed. Mean blood pressure was recorded immediately, and 30, 60, and 90 minutes after spinal anesthesia, after transfer to the post anesthesia care unit. RESULTS: No significant differences in demographic data (age, height, weight, operation time, nausea, and vomiting) were observed between the two groups. The intraoperative fluid volume of the celecoxib group was lower than that of the control group (782.8+/-240.6 vs 1382.4+/-369.2; P<0.05). No differences in hemodynamic changes (intraoperative blood pressure) were observed between the two groups. CONCLUSION: Perioperative use of an inhibitor of cyclooxygenase 2 is an effective component of multimodal analgesia, which has no effect on hemodynamic change and side effects during TKA.

Effects of cyclooxygenase-2 inhibitor on doxorubicin chemosensitivity in leukemia HL-60 cell line / 白血病·淋巴瘤

Objective To evaluate the enhancement of chemosensitivity of celecoxib, a specific cyclooxygenase-2 (COX-2) inhibitor, on leukemia HL-60 cell line in vitro, and explore the possible mechanisms. Methods MTT assay was used to assess the cytostatic efficacy of doxorubicin in the absent or present of different doses of celecoxib on HL-60 cell. The apoptosis of HL-60 cells was measured by flow cytometry (FCM). Gene expressions of Survivin was examined by reverse transcription-polymerase chain reaction (RT-PCR). Protein of survivin was detected by Western blotting. Results Celecoxib could increase the cytostatic efficacy of doxorubicin on HL-60 cells. HL-60 cells were treated with increasing doses of doxorubicin in absence or presence of celecoxib (5 μmol/L, 10 μmol/L), IC50 were 0.48 μg/ml, 0.25 μg/ml and 0.16 μg/ml, respectively. Doxorubicin combined with low dose of celecoxib could induce the down-regulation of mRNA and protein of Survivin. Apoptosis rate of HL-60 cells treated with both 0.10 μg/ml doxorubicin and celecoxib(5 μmol/L, 10 μmol/L) were (13.07±1.66) % and (22.36±1.84) %, respectively, while it was (5.72±1.25) % in HL-60 cells treated with 0.10 μg/ml doxorubicin alone, with significant difference (P＜0.01).Conclusion Celecoxib could enhance the chemosensitivity of doxorubicin on leukemia HL-60 cell, which involves in increasing the apoptosis of HL-60 cells by down-regulation expression of Survivin.

Inhibitory effect of selective cyclooxygenase-2 inhibitor NS-398 on proliferation and invasion of human colorectal cancer cells / 第二军医大学学报

Objective: To investigate the effect of NS-398, a selective cyclooxygenase-2 (COX-2) inhibitor, on the proliferation and invasion of human colon carcinoma cells in vitro, so as to determine the possibility of COX-2 as a new target for treatment of colon carcinoma. Methods: The expression of COX-2 in colorectal cancer cells (CW-2, COLO-320) was detected by RT-PCR and Western blotting. COLO-320 cell proliferation was measured by MTT after treatment with NS-398. Cell invasion ability was measured using migration and invasion chamber systems. Western blotting assay was used to examine the influence of NS-398 on MMP 2 expression. Results: Our results showed that CW-2, COLO-320 cells expressed COX-2 mRNA and protein. NS-398 inhibited the proliferation of COLO-320 cells in a time and concentration-dependent manner. Invasion test showed that NS-398 inhibited the migration and invasion of COLO-320 cells. Western blotting revealed that NS-398 inhibited the expression of MMP-2 in COLO-320 cells. Conclusion: The selective COX-2 inhibitor NS-398 can inhibit COLO-320 cell proliferation and invasion, indicating COX-2 may serve as a new target for colon carcinoma treatment.

Inhibitory Effect of IFN-beta, on the Antitumor Activity of Celecoxib in U87 Glioma Model

OBJECTIVE: Interferon-beta, (IFN-beta) has been used in the treatment of cancers. Inhibition of the enzyme cyclooxygenase (COX) with celecoxib had a significantly suppressive effect on tumor growth, angiogenesis, and metastasis in a variety of tumors. The aim of this study was to elucidate the antiglioma effect of combined treatment with IFN-beta and celecoxib in U87 glioma model. METHODS: The in vitro effects of IFN-beta (50-1,000 IU/mL) and celecoxib (50-250 micrometer) alone or combination of both on the proliferation and apoptosis of U87 cells were tested using MTT assay, FACS analysis and DNA condensation. To determine the in vivo effect, nude mice bearing intracerebral U87 xenograft inoculation were treated with IFN-beta intraperitoneally (2x10(5) IU/day for 15 days), celecoxib orally (5, 10 mg/kg) or their combination. RESULTS: IFN-beta or celecoxib showed an inhibitory effect on the proliferation of U87 cells. When U87 cells were treated with IFN-beta and celecoxib combination, it seemed that IFN-beta interrupted the antiproliferative and apoptotic activity of celecoxib. No additive effect was observed on the survival of the tumor bearing mice by the combination of IFN-beta and celecoxib. CONCLUSION: These results suggest that IFN-beta seems to inhibit the antiglioma effect of celecoxib, therefore combination of IFN-beta and celecoxib may be undesirable in the treatment of glioma.

Fetal ductus arteriosus constriction and heart failure following maternal cyclooxygenase-2 inhibitor ingestion: A case report / 대한산부인과학회지

We report a case of premature constriction of the fetal ductus arteriosus following maternal ingestion of a cyclooxygenase-2 (COX-2) inhibitor at 37 weeks' gestation. Fetal sonography at 38+2 weeks' gestation revealed tricuspid regurgitation, absent transpulmonary valve flow, right heart enlargement, and pericardial effusion. An immediate delivery resulted in a good postnatal outcome with dramatic improvement in the clinical and echocardiographic findings. Maternal exposure to Non-steroidal anti-inflammatory drugs (NSAIDs), especially late in gestation, can cause premature constriction of the ductus arteriosus, heart failure, and fetal death. Therefore, the use of NSAIDs late in gestation should be considered in limited cases with close fetal heart monitoring.

Synergistic inhibitory effect of nimesulide in combination with 5-fluorouracil on gastric cancer cells and its possible mechanisms / 中华消化杂志

Objective To investigate the inhibitory effects of combined treatment of nimesulide, a selective cyclooxygenase-2 inhibitor, with 5-fluorouracil (5-FU) on gastric cancer cell lines and its pos-sible mechanisms. Methods The human gastric cancer cell lines MKN45 and MKN28 were used in the study. After 48 hours treatment with nimesulide or 5-FU alone or in combination, the cells growth was determined by MTT assay. Flow cytometry and FITC-Annexin-V/PI kit were used to determine the effect of drugs on the cell cycle and the apoptosis of gastric cancer cells. The expression of COX-2 mRNA was detected by RT-PCR. The expressions of apoptosis-associated protein Bax and Bcl-2 were detected by Western blotting. Results Different level of COX-2 mRNA expression was observed in MKN45 and MKN28 cell lines. Treatment of the two cell lines with nimesulide in combination with 5-FU can significantly reduce the expression of COX-2 mRNA. Nimesulide could inhibit the growth and induce apoptosis of gastric cells. Combined treatment of nimesulide with 5-FU resulted in a synergistic effect of inhibiting growth and inducing apoptosis. The synergistic inhibiting effect on cell growth was irrespective of treatment sequence, but the highest cytotoxity was obtained when the cell lines were treated with two drugs simultaneously. Treatment with 5-FU enhanced expression of the pro-apoptotic gene Bax, while nimesulide reduced expression of the anti-apoptotic gene Bcl-2, resulting in a significantly higher ratio of Bax-to-Bcl-2. Conclusions The combined treatment of nimesulide with 5-FU results in synergistic inhibiting effect on growth of gastric cancer cell lines, and inducing apoptosis by enhanced Bax-to-Bcl-2 ratio and suppression of COX-2 mRNA expression may be the mechanisms.

The study of selective cyclooxygenase-2 inhibitor NS-398 on proliferation and apoptosis of human colon cancer cells / 中华消化杂志

Objective To investigate the influence of NS-398, a selective cyclooxygenase(COX)-2 inhibitor, on the proliferation and apoptosis of colorectal cancer cell HT-29, and to explore its potential mechanism. Methods Cultured HT-29 cells were treated with NS-398. MTT assay and flow cytometry were used to measure the proliferation and apoptosis. RT-PCR analysis was performed to measure the level of COX-2 mRNA expression at different time points in HT-29 cells. The expression of prostaglandin (PG)E2,Cyclin D1 and Bcl-2 were measured by ELISA and Western blot, respectively.Results High expression of COX-2 mRNA was detected in colorectal cancer cell line HT-29 and no obvious change of COX-2 mRNA was found after the treatment of NS-398 . NS-398 inhibited the cells proliferation and induced apoptosis in a dose-and time-dependent manner, and resulted in a significant down-regulation of Cyclin D1, Bcl-2 and PGE2.Conclusions Our results show that NS-398 may inhibit the proliferation and induce apoptosis of colon cancer cell lines HT-29 through decreasing expression of Cyclin D1 and Bcl-2 . COX-2 activity rather than its mRNA expression was related to NS-398-mediated pathway on HT-29 cells. This may be a new interfering target of selective COX-2 inhibitor on colon cancer.

Chemopreventive effects of celecoxib on rat colon aberrant crypt foci induced by dimethylhydrazine / 中华消化杂志

Objective An investigation was conducted to assess the chemopreventive effects of celecoxib, a selective cyclooxygenase(COX)-2 inhibitor, on a rat colon carcinogenesis model induced by dimethylhydrazine (DMH). The results were compared with those of sulindac. Methods Thirty-two 8-week-old female Sprague-Dawley rats were randomly divided into four groups (n=8 each):Group A rats were treated with DMH(120 mg/kg wt, single subcutaneous injection) alone and group B rats were treated with saline alone. Group C rats were pre-treated with sulindac (320 mg/kg feedstuff) and group D rats pre-treated with celecoxib (1500 mg/kg feedstuff) for 7 days before DMH initiation. The animals were killed at the end of the experiment (week 5) and the aberrant crypt foci(ACF) and aberrant crypt(AC) of the colonic mucosa were assessed after being stained with methylene blue. Results In group A(DMH only), the average numbers of ACF and AC were 182.4?93.43 and 262.8?197.8 respectively. In group B (saline group) rats, no ACF was found. In group C (sulindac group) rats, the average numbers of ACF and AC were 91.25?48.98 and 139.60?68.52 respectively, both of them were decreased significantly as compared with those in Group A (P

Chemoprevention of gastric cancer by specific cyclooxygenase-2 inhibitor in rats / 中华消化杂志

Objective To examine the chemo-preventive effect of cyclooxygenase-2(COX-2) inhibitor (celecoxib) in an animal model of stomach carcinogenesis. Methods Eighty-six male Wistar rats were divided into six groups. The rats were given water alone (group A, n=5), N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) (group B, n=16), 3 mg/kg of indomethacin daily (group C, n=16), 5 mg/kg of celecoxib daily (group D, n=17), 10 mg/kg of celecoxib daily (group E, n=16) or 20 mg/kg of celecoxib daily (group F, n=16). The animals in group B to F were given 10% sodium chloride (in the initial 6 weeks) and drinking water containing MNNG (100 ?g/ml) to induce gastric adenocacinoma. All animals received treatment for 40 weeks, and were sacrificed after death or at week 48. Gastric tumor was evaluated histologically. Results Among 86 rats, 26 rats died, and 60 rats completed the experiment. The incidences of gastric cancer were found 0 (0%) in group A, 12 (75.0%) in group B, 11 (68.8%) in group C, 12 (70.6%) in group D, 3(18.8%) in group E, and 5(31.3%) in group F. There were significant differences in tumor incidence (P=0.002), multiplicity (P=0.001) and volume (P=0.009) among different groups. When compared with group B, the group E had the greatest reduction in tumor incidence (P=0.004), tumor multiplicity ( P=0.006) and mean tumor volume (P=0.02). Treatment with indomethacin had no significant effect on tumor development. Conclusion While treatment with indomethacin had no significant effect on tumor development, treatment with celecoxib reduced gastric cancer incidence and growth in rats.

Effect of nimesulide on chemoprevention of N-ethyl-N-nitro-N-nitrosoguanidine-induced gastric cancer in rat model / 中华消化杂志

Objective To investigate the effect of nimesulide,a selective cyclooxygenase (COX)-2 inhibitor,on the chemoprevention of N-ethyl-N-nitro-N-nitrosoguanidine (ENNG)-induced gastric cancer in rat model. Methods Ninety-six male Wistar rats were randomized to drink the solution of ENNG (group M), ENNG/low dose nimesulide (group MN_L), ENNG/ high dose nimesulide (group MN_H), low dose nimesulide (group N_L), high dose nimesulide (group N_H) or water (group P). Eighty-nine(92.7%) rats completed the study and were sacrificed at (28?2) weeks. The animals were assessed for the presence of gastric cancer, COX-2 expression and precancerous changes in gastric mucosa. Results The incidence of gastric carcinoma in group M was 56.3% (9 /16), significantly higher than 7.4%(1/14)in MN_L group and 6.3%(1/16)in MN_H group( P

A study on the mechanisms of apoptosis of gastric cancer line induced by Nimesulide / 中华消化杂志

Objective Non steroidal anti inflammatory drugs(NSAIDs)can induce apoptosis in gastric cancer cell and the mechanism is not clear. We aimed to study the mechanism of selective COX 2 inhibitor Nimesulide induced apoptosis of human gastric cancer line SGC 7901 by detecting the expressions of COX 2 at mRNA level, c myc, Bcl 2 and caspase 3 at protein level. Methods Apoptosis was determined by electronic microscopy, Annexin V FITC staining and flow cytometry. The mRNA of COX 2 was detected by RT PCR. The protein expressions of c myc, Bcl 2 and caspase 3 were examined by immunohistochemistry. Results Nimesulide of 50 ?mol/L at 48 and 72 h, and of 100 ?mol/L and 200 ?mol/L at 24, 48 and 72 h induced apoptosis of gastric cancer cells in a dose and time dependent manner.Their apoptotic rates were 7.51%, 9.86% and 11.58%, 12.45%, 16.66% and 12.21%, 15.38%, 20.28% respectively. It increased c myc and caspase 3 expression and decreased Bcl 2 expression and COX 2 mRNA expression. The positive protein expression rates of Bcl 2, c myc and capase 3 were (20.2?7.6)%,(49.2?15.1)% and (34.6?12.9)% respectively with Nimesulide of 200 ?mol/L at 72 h,while the controls being (44.6?12.1)%, (24.7 ?9.5)% and (14.8?6.4)% the three comparative P