Celecoxib

摘要： BACKGROUND Anti-inflammation drugs were uncovered to be a potential therapy for depression.Celecoxib as a selective COX2 inhibitor is also one anti-inflammation drugs.Celecoxib is widely used in the clinic,which is well known by medical workers.It is uncertain whether celecoxib has efficacy in improving depression.AIM To estimate the effect of celecoxib on improving depression.METHODS All literature was searched until 2022.The databases included PubMed,OVID database,Cochrane library,Web of Science,CNKI,Clinicaltrials.gov database and Wanfang database.The random effects model was used to estimate the standardized mean differences with 95%CIs.With determined diagnostic criteria,studies containing patients with depression in the celecoxib group and the control group were included in the meta-analysis.The primary outcome measures were set for depression scale scores.RESULTS Twenty-nine randomized controlled studies were included in the meta-analysis(including 847 subjects with depression and 810 control subjects).The metaanalysis showed that celecoxib had an effect of anti-depression.At the same time,heterogeneity was observed(I2=82.1%,P=0.00),and meta-regression was implemented to estimate the source of heterogeneity,which showed that the type of depression scale and depression type may lead to the heterogeneity.Subgroup analysis with respect to depression scale and depression type suggested that depression type was the possible main source of heterogeneity.Moreover,Egger’s test,Begg’s test,funnel plot and Doi plot was implemented,and publication bias was found to be significant.Next,the trim and fill method was used to estimate the influence of publication bias on the outcome of the meta-analysis,which showed that the outcome of the meta-analysis was reliable.Sensitivity analysis was estimated by deleting a study one by one,and the outcome of the meta-analysis was significantly stable.The quality of all randomized controlled trial studies was assessed by risk of bias,which indicated the rank of evidence in the meta-analysis was high.CONCLUSION Celecoxib could be effective for improving depression.

摘要： BACKGROUND Pelvic lipomatosis(PL)is a rare benign condition with characteristic overgrowth of histologically benign fat and invasion and compression of pelvic organs,often leading to non-specific lower urinary tract symptoms(LUTS).Approximately 40%of patients with PL have cystitis glandularis(CG).The cause of PL combined with CG is poorly understood,and there is currently no effective treatment.Refractory CG with upper urinary tract obstruction even requires partial or radical bladder resection.CASE SUMMARY In this case,a patient suffering from PL with CG was treated by transurethral resection of bladder tumour(TUR-BT)and oral administration of celecoxib,a selective cyclooxygenase-2(COX-2)inhibitor.The LUTS were alleviated,and the cystoscopy results improved significantly.Immunohistochemistry showed upregulated COX-2 expression in the epithelium of TUR-BT samples,suggesting that COX-2 may participate in the pathophysiological process of PL combined with CG.CONCLUSION We report for the first time that celecoxib may be an effective treatment strategy for PL combined with refractory CG.

摘要： BACKGROUND Chronic atrophic gastritis(AG)with intestinal metaplasia(IM)significantly increases the risk of gastric cancer.Some medicines have showed definite therapeutic effects in AG and IM regression.AIM To validate the efficacy of Lamb’s tripe extract and vitamin B12 capsule(LTEVB12)initial therapy and celecoxib rescue therapy for IM and AG.METHODS A total of 255 patients were included to receive LTEVB12 initial therapy(2 capsules each time,three times daily for 6 mo)in hospital in this study.The patients with failure of IM regression continued to receive celecoxib rescue therapy(200 mg,once daily for 6 mo).After each therapy finished,the patients underwent endoscopy and biopsy examination.The regression efficiency was assessed by the operative link on gastritis assessment(OLGA)and the operative link on the gastric intestinal metaplasia assessment(OLGIM)staging system.Logistic regression analysis was applied to identify factors associated with the curative effect.RESULTS For LTEVB12 initial therapy,the reversal rates of IM and AG were 52.95%and 48.24%,respectively.Analogously,for celecoxib rescue therapy,the effective rates for IM and AG were 56.25%and 51.56%,respectively.The IM regression rate of complete therapy was up to 85.03%.In different OLGA and OLGIM stages of IM patients,therapeutic efficiency showed a significant difference in each group(P<0.05).For both therapies,patients with high stages(III or IV)of both the OLGA and OLGIM evaluation systems showed a higher IM or AG regression rate than those with low stages(I or II).Among patients with high stages(OLGIM III and IV),the IM regression rate was above 70%for each therapy.Eating habits,fresh vegetable intake,and high-salt diet were identified as independent factors for the IM reversal effect of LTEVB12 therapy,especially high-salt diet(odds ratio=1.852,P<0.05).CONCLUSION Monotherapy could reverse IM and AG.LTEVB12 initial therapy and celecoxib rescue therapy significantly increase the regression effect.IM may not be the point of no return among gastric precancerous lesions.

摘要： BACKGROUND Endoplasmic reticulum(ER)stress is an important mechanism in the progression of chronic and acute liver diseases,especially in the progression and recovery of liver fibrosis.Excessive and long-term ER stress induces apoptosis.ER stressinduced apoptosis is considered to be an important pathway in the development of liver fibrosis.Cyclooxygenase-2(COX-2)induction is also closely related to ER stress.In our previous studies,we showed that celecoxib,a COX-2 inhibitor,improves liver fibrosis and portal hypertension.However,the role and mechanism of celecoxib in alleviating liver fibrosis remain unclear.AIM To investigate whether celecoxib alleviates liver fibrosis by inhibiting hepatocyte apoptosis via the ER stress response.METHODS Cirrhosis was induced by intraperitoneal injections of thioacetamide(TAA)for 16 wk(injection dose is 200 mg/kg per 3 d for the first 8 wk and 100 mg/kg per 3 d after 8 wk).Thirty-six male Sprague-Dawley rats were randomly divided into three groups,namely,control group,TAA group,and TAA+celecoxib group.In the last 8 wk,TAA-induced cirrhotic rats received celecoxib(20 mg/kg/day)or the vehicle by gastric gavage.After 16 wk,the rats were sacrificed,and serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),and albumin(ALB)were detected.The hepatic fibrosis areas were evaluated by Sirius red staining and the degree of fibrosis was assessed by measuring the level of hydroxyproline.ER stress levels were evaluated by detecting the marker proteins glucose-regulated protein 78(GRP78),CCAAT/enhancer binding protein homologous protein(CHOP),PKR-like ER protein kinase(PERK),activating transcription factor 6(ATF6),and inositol-requiring enzyme 1 alpha(IRE1α).Apoptosis levels were evaluated by detecting caspase-12 and caspase-3.RESULTS The serum ALT and AST levels in the liver were significantly reduced by celecoxib;however,the serum ALB had no significant changes.Celecoxib significantly reduced the degree of liver fibrosis and the levels of hydroxyproline(-38%and-25.7%,respectively,P<0.01).Celecoxib ameliorated ER stress by reducing the level of GRP78 compared to the TAA group(P<0.05).Consistently,after celecoxib administration,the upregulation of TAA-induced hepatic apoptosis markers(caspase-12 and caspase-3)and CHOP were significantly inhibited.In addition,after celecoxib treatment,the expression of key molecules associated with ER stress(PERK,ATF6,and IRE1)was decreased(P<0.05).CONCLUSION Therapeutic administration of celecoxib effectively reduces hepatic apoptosis in TAA-induced cirrhotic rats.The mechanism of action may be attributed to the suppression of CHOP expression,which subsequently inhibits ER stress.

摘要： 目的:探讨选择性环氧合酶-2(COX-2)抑制剂Celecoxib联合羟基喜树碱对缺氧诱导的人肝癌细胞株SMMC-7721细胞增殖和凋亡的影响.方法:应用三气培养箱在缺氧环境下培养人肝癌细胞株SMMC-7721细胞.预实验筛选Celecoxib、羟基喜树碱最小有效终浓度,设24、48、72小时为干预时间并筛选最佳作用时间.分别以Celecoxib及羟基喜树碱单独实验筛选的最小有效浓度为联合组浓度;以Celecoxib单独实验筛选最佳作用时间为实验时间.倒置显微镜观察细胞形态学变化;应用四氮唑盐比色法(MTT法)监测细胞增殖活力;Annexin V/PI双染色法检测细胞凋亡;免疫细胞化学法(SP法)检测凋亡蛋白Bax、Bcl-2、COX-2的表达.结果:不同浓度Celecoxib及不同时间对SMMC-7721细胞表现出的生长抑制作用呈剂量依赖性及时间依赖性.Celecoxib(30 mg/L)单用在作用72 h时即可抑制SMMC-7721细胞的增殖.选72 h为作用时间,不同浓度羟基喜树碱对SMMC-7721细胞表现出的生长抑制作用呈剂量依赖性,浓度为0.625μmol/L羟基喜树碱即可抑制SMMC-7721细胞的增殖.选用羟基喜树碱(0.625μmol/L)与Celecoxib(30 mg/L)联合作用72 h时,联合抑制作用结果呈现协同作用(Q>1.15).流式细胞仪检测分析,两种药物均可有效诱导SMMC-7721细胞的凋亡,并且在上述浓度联合作用时具有协同效应.免疫细胞化学结果显示,Cele-coxib(30 mg/L)组和联合用药组细胞质内棕黄色颗粒较对照组染色浅,表明Bcl-2和COX-2蛋白表达有所下降,而Bax蛋白表达在Celecoxib(30 mg/L)和联合用药组中黄色颗粒的阳性细胞较对照组增多,表明Bax蛋白表达有所上调;并且此变化与Celecoxib(30 mg/L)组比较联合用药组有协同作用(P<0.05).结论:缺氧状态下Celecoxib与羟基喜树碱对SMMC-7721细胞株均有抑制增殖与促进凋亡作用,并且两者联合作用有协同作用;Celecoxib的作用机制除了抑制COX-2外,还可能与下调Bcl-2、上调Bax的表达有关.

摘要： AIM To counteract/reveal celecoxib-induced toxicity and NO system involvement. METHODS Celecoxib(1 g/kg b.w. ip) was combined with therapy with stable gastric pentadecapeptide BPC 157(known to inhibit these lesions, 10 μg/kg, 10 ng/kg, or 1 ng/kg ip) and L-arginine(100 mg/kg ip), as well as NOS blockade [N(G)-nitro-L-arginine methyl ester(L-NAME)](5 mg/kg ip) given alone and/or combined immediately after celecoxib. Gastrointestinal, liver, and brain lesions and liver enzyme serum values in rats were assessed at 24 h and 48 h thereafter. RESULTS This high-dose celecoxib administration, as a result of NO system dysfunction, led to gastric, liver, and brain lesions and increased liver enzyme serum values. The L-NAME-induced aggravation of the lesions was notable for gastric lesions, while in liver and brain lesions the beneficial effect of L-arginine was blunted. L-arginine counteracted gastric, liver and brain lesions. These findings support the NO system mechanism(s), both NO system agonization(L-arginine) and NO system antagonization(L-NAME), that on the whole are behind all of these COX phenomena. An even more complete antagonization was identified with BPC 157(at both 24 h and 48 h). A beneficial effect was evident on all the increasingly negative effects of celecoxib and L-NAME application and in all the BPC 157 groups(L-arginine + BPC 157; L-NAME + BPC 157; L-NAME + L-arginine + BPC 157). Thus, these findings demonstrated that BPC 157 may equally counteract both COX-2 inhibition(counteracting the noxious effects of celecoxib on all lesions) and additional NOS blockade(equally counteracting the noxious effects of celecoxib + L-NAME). CONCLUSION BPC 157 and L-arginine alleviate gastrointestinal, liver and brain lesions, redressing NSAIDs' post-surgery application and NO system involvement.

摘要： Objective:to study the influence and possible mechanism of celecoxib on ventricular structure and function in normal rats. Methods:Non-invasive measurement of arterial blood pressure, changes in blood pressure was observed. Echocardiographic assessment of ventricular function change. HE staining left ventricular ventricular structure changes observed in rats. Plasma and myocardial tissue TNF-α,IL-10,PGI 2,TXA 2 content Elisa assay;TUNEL assay ventricular myocardial cell apoptosis. Results:4 week' s treatment later, Celecoxib medication EF and FS after 2 weeks increased significantly ( P<0 . 05 ) , plasma TNF-α lower ( P<0 . 05 ) , myocardial tissue PGI 2 increased ( P<0. 05),TXA 2 reduction(P<0. 05)CO increased(P<0. 05);PGI 2 decreased plasma TXA 2 increased (P<0. 05),IL-10 reduced(P<0. 05). Conclusion:Celecoxib can be improved left ventricular systolic function,you can adjust the local equilibrium heart PGI 2/TXA 2,as well as to adjust the overall TNF-α,IL-10 content.%目的：探讨塞来昔布( Celecoxib)对正常Wister大鼠心室结构和功能的影响及可能的作用机制。方法：无创测动脉血压,观察血压变化。超声心动图评价心室功能的改变。左心室组织切片苏木精-伊红( HE)染色观察大鼠心室结构的变化。 ELISA法检测血浆及心肌组织中肿瘤坏死因子-α( TNF-α)、白细胞介素-10(IL-10)、前列环素(PGI2)、血栓素A2(TXA2)的含量；TUNEL法检测左心室心肌细胞凋亡情况。结果：Celecoxib用药2wk后射血分数(EF)和左心室短轴缩短率(FS)显著升高(P<0.05),血浆中TNF-α显著降低(P<0.05),心肌组织中PGI2显著增加(P<0.05),TXA2显著减少(P<0.05)；用药4wk后CO显著升高(P<0.05)；PGI2减少,血浆中TXA2显著升高(P<0.05),IL-10显著降低(P<0.05)。结论：Celecoxib可使大鼠左心室收缩功能有所提高,可以调节心脏局部前列环素和血栓素A2的比例平衡,同时调节整体TNF-α、IL-10含量。

摘要： 目的:探讨塞来昔布（Celecoxib）对正常Wister大鼠心室结构和功能的影响及可能的作用机制。方法:无创测动脉血压,观察血压变化。超声心动图评价心室功能的改变。左心室组织切片苏木精-伊红（HE）染色观察大鼠心室结构的变化。ELISA法检测血浆及心肌组织中肿瘤坏死因子-α（TNF-α）、白细胞介素-10（IL-10）、前列环素（PGI2）、血栓素A2（TXA2）的含量;TUNEL法检测左心室心肌细胞凋亡情况。结果:Celecoxib用药2wk后射血分数（EF）和左心室短轴缩短率（FS）显著升高（P<0.05）,血浆中TNF-α显著降低（P<0.05）,心肌组织中PGI2显著增加（P<0.05）,TXA2显著减少（P<0.05）;用药4wk后CO显著升高（P<0.05）;PGI2减少,血浆中TXA2显著升高（P<0.05）,IL-10显著降低（P<0.05）。结论:Celecoxib可使大鼠左心室收缩功能有所提高,可以调节心脏局部前列环素和血栓素A2的比例平衡,同时调节整体TNF-α、IL-10含量。

摘要： Objective To study the effect and related mechanism of celecoxib on tumor necrosis factorrelated apoptosis-inducing ligand(TRAIL) induced apoptosis of medullary thyroid cancer TT cell line.Methods MTT assay was used to measure the growth inhibition induced by TRAIL and celecoxib alone and their combination.TT cell cycle distribution was analyzed by flowcytometry.Hochest33258 staining and DNA ladder was used to detect the apoptosis of drug combination on TT cells.Western blot was used detect the protein change of cyclin A,Cdk2,caspase-8,c-FLIP,and RIP.Results ①MTT showed the growth inhibition ratio of TT cell intervened by the combination of TRAIL and celecoxib was 47.53％ ± 1.34％,which was much higher than that intervened by TRAIL(7.75 ％ ± 3.84％)and celecoxib alone.The differences had statistical significance (t test,F =5.234,P ＜0.01);②PI detection found the cells' number in G0/G1 phase in celecoxib group and combination group were increased compared to that in control group and TRAIL group(F =242.694,P ＜ 0.01);③Western blot indicated the expression of Cyclin A and Cdk2 were down regulated,there was no statistic significance;④ The apoptosis morph in nuclus was detected by Hochest33258 staining and showed the karyopycnosis and muclear fragmentation were increased in combination group with the apoptosis rate 24.23％ ± 2.91％,which was much higher than that in TRAIL(5.86％ ± 1.41％) and celecoxib(20％ ± 1.24％) (t test,F =1.824,P ＜0.01),the difference has statistic significance;⑤Western blot illustrated the active schizolysis of casplase-8 was higher and the expression of c-FLIP and RIP was down regulated in combination group.Conclusion celecoxib plays a positive effect on TRAIL-reduced apoptosis of medullary thyroid cancer TT cell line,which may due to the cell cycle arrest at G0/G1 phase,down-regulation of c-FLIP and RIP and subsequent activation of caspase-8.%目的 探讨塞来昔布(celecoxib)增强肿瘤坏死因子相关凋亡诱导配体(tumor necrosis factor-related apoptosis-inducing ligand,TRAIL)诱导甲状腺髓样癌TT细胞凋亡的效应及相关机制.方法 MTT法检测TRAIL、celecoxib及2者联合应用对TT细胞的增殖作用;PI单染流式细胞仪检测联合用药对TT细胞周期的影响;Hochest33258染色和DNA ladder检测联合用药对TT细胞凋亡的作用;Western blot检测cyclin A、Cdk2、caspase-8、c-FLIP、RIP蛋白表达改变.结果 ①MTT实验显示:TRAIL1000 ng/ml与celecoxib 50 μM联合用药的增殖抑制率为(47.53％±1.34％),明显高于单用TRAIL(7.75％±3.84％)及celecoxib (24.49％±1.57％)之和组(t检验,F=5.234,P＜0.01),差异有统计学意义;②PI检测显示:celecoxib组和联合用药组G0/G1期细胞明显高于Control组和TRAIL组(F=242.694,P＜0.01);③Westem blot检测:celecoxib组及联合用药组Cyclin A和Cdk2蛋白表达明显下调,且2者之间未见明显差异;④Hochest33258染色观察细胞核的凋亡形态学改变发现:联合用药组核固缩及核碎裂现象明显增多,其细胞凋亡率为(24.23％±2.91％),明显高于单用TRAIL(5.86％±1.41％)及celecoxib 11 (20％±1.24％)之和(t检验,F=1.824,P＜0.01),差异具有统计学意义;⑤Western blot检测发现:联合用药组caspase-8活化裂解程度明显增加,c-FHP及RIP蛋白表达亦明显下调.结论 celecoxib能增强TRAIL对甲状腺髓样癌TT细胞增殖的抑制作用,其机制是通过celecoxib将TT细胞阻滞于G0/G1期,并下调c-FHP及RIP的表达,促进TRAIL对caspase-8的活化,诱导细胞凋亡.

摘要： Background: The human serine palmitoyltransferase-1, SPTLC1, subunit is emerging as a stress responsive protein with putative role in modulating cellular stress response behavior. When compared to the parental cell line, recombinant Glioma cells expressing C-terminal modified SPTLC1 are found to show resistance to the cytotoxic effect of polycyclic hydrocarbons, PHs, including the environmental contaminant 3-methylcholanthrene. This novel functional association of SPTLC1 expression with proliferative capacity is thought to be due, in part, to its ability for crosstalk with protein regulators of different biological processes. Whether the effect of SPTLC1 on sensitivity to PHs extends to therapeutic drugs and the progression of the malignant phenotype is of research interest. Methods: In the current study, sub-cellular localization was by immunostaining for SPTLC1 in untreated and chemical treated cells and detection with confocal microscopy. The effect expressing C-terminal modified SPTLC1, in cancer cell lines of the inflammation-associated type, has on chemosensitivity and gene expression was also assessed. Parent Glioma LN18 and SKN-SH cells and their SPTLC1 recombinants were each treated with Glutamate, an excitatory neurotransmitter that can participate in both neuronal and excitotoxic signaling. In addition to the Glioma and SKN-SH cells, the PC3 prostate cancer and 647V bladder cancer cell lines were also treated with Celecoxib, a potent inhibitor of cyclooxygenase 2, COX-2, and an anti-inflammatory drug recently found to have anti-neoplastic activity against several malignancies. Results: Confocal microscopy revealed that Celecoxib mediates both rapid and enhanced redistribution of SPTLC1 and COX-2, to focal adhesion sites. In cell viability assay, SPTLC1 recombinant cells exhibited differential but dose-dependent resistance to excitotoxic levels of Glutamate. Drug co-treatment with a non-lethal dose of the potent kinase inhibitor, Sulfasalazine, increased the anti-proliferation effect of Celecoxib in a dose-dependent manner for all the cell lines tested. Conclusions: The effect of SPTLC1 expression on cellular chemosensitivity seen in the present study further highlights possible role of a C-terminal modified SPTLC1 variant in the biologic modulation of cellular behavior in response to therapeutic anticancer drugs.

摘要： 本发明涉及组蛋白脱乙酰酶(HDAC)抑制剂，呈酸性盐形式的西达本胺(chidamide)，及非类固醇抗炎药物(NSAIDs)，呈碱性盐形式的塞来昔布(celecoxib)的组合。本发明亦关于显著调节肿瘤微环境并因此显著改善抗癌活性的方法。

摘要： 本发明提供一种药物组合物,它含有一种或多种可口服释放的剂量单位,每个剂量单位含有约10mg－1000mg的celecoxib颗粒和一种或多种可药用赋形剂的致密混合物。所述组合物可用于治疗或预防环加氧酶－2介导的疾病。