In this study, PC12 Adh cells and Neuro-2a cells were treated with Rho-associated kinase inhibitors （Y27632 and Fasudil）, a cyclooxygenase-1 selective inhibitor （SC560）, and a cyclooxygenase-2 inhibitor （NS398）....In this study, PC12 Adh cells and Neuro-2a cells were treated with Rho-associated kinase inhibitors （Y27632 and Fasudil）, a cyclooxygenase-1 selective inhibitor （SC560）, and a cyclooxygenase-2 inhibitor （NS398）. We found that these cells became tolerant to Rho-associated kinase inhibitors, as neurite outgrowth induced by these inhibitors diminished following more than 3 days of exposure in either cell line. The proteins cyclooxygenase-2 and cytosolic prostaglandin E synthetase were upregulated at day 3. NS398 decreased the tolerance to neurite outgrowth induction in both cell lines, whereas SC560 had almost no effect. These findings indicate that cells become tolerant to neurite outgrowth induced by Rho-associated kinase inhibitors, this is at least partly associated with upregulation of proteins involved in the cyclooxygenase-2 pathway, and cyclooxygenases-2 inhibition prevents this tolerance.展开更多
AIM: To evaluate the opioid-sparing effect of selective cyclooxygenase-2(COX-2) inhibitors on short-term surgical outcomes after open colorectal surgery.METHODS: Patients undergoing open colorectal resection within an...AIM: To evaluate the opioid-sparing effect of selective cyclooxygenase-2(COX-2) inhibitors on short-term surgical outcomes after open colorectal surgery.METHODS: Patients undergoing open colorectal resection within an enhanced recovery after surgery protocol from 2011 to 2015 were reviewed. Patients with combined general anesthesia and epidural anesthesia, and those with acute colonic obstruction or perforation were excluded. Patients receiving selective COX-2 inhibitor were compared with well-matched individuals without such a drug. Outcome measures included numeric pain score and morphine milligram equivalent(MME) consumption on postoperative day(POD) 1-3, gastrointestinal recovery(time to tolerate solid diet and time to defecate), complications and length of postoperative stay.RESULTS: There were 75 patients in each group. Pain score on POD 1-3 was not significantly different between two groups. However, MME consumption and MME consumption per kilogram body weight on POD 1-3 was significantly less in patients receiving a selective COX-2 inhibitor(P < 0.001). Median MME consumption per kilogram body weight on POD 1-3 was 0.09, 0.06 and nil, respectively in patients receiving a selective COX-2 inhibitor and 0.22, 0.25 and 0.07, respectively in the comparative group(P < 0.001), representing at least 59% opioidreduction. Patients prescribing a selective COX-2 inhibitor had a shorter median time to resumption of solid diet [1(IQR 1-2) d vs 2(IQR 2-3) d; P < 0.001] and time to first defecation [2(IQR 2-3) d vs 3(IQR 3-4) d; P < 0.001]. There was no significant difference in overall postoperative complications between two groups. However, median postoperative stay was significantly 1-d shorter in patients prescribing a selective COX-2 inhibitor [4(IQR 3-5) d vs 5(IQR 4-6) d; P < 0.001]. CONCLUSION: Perioperative administration of oral selective COX-2 inhibitors significantly decreased intravenous opioid consumption, shortened time to gastrointestinal recovery and reduced hospital stay after open colorectal surgery.展开更多
The discovery of COX-2 provides a novel target developing more effective NSAIDs with fewer side effects. On the basis of results from the structure-activity relationships (SAR) of selective COX-2 inhibitors, we have d...The discovery of COX-2 provides a novel target developing more effective NSAIDs with fewer side effects. On the basis of results from the structure-activity relationships (SAR) of selective COX-2 inhibitors, we have designed and synthesized some promising compounds.展开更多
Background Gene therapy by adenovirus-mediated wild-type p53 gene transfer has been shown to inhibit lung cancer growth in vitro,in animal models,and in human clinical trials.The antitumor effect of selective cyclooxy...Background Gene therapy by adenovirus-mediated wild-type p53 gene transfer has been shown to inhibit lung cancer growth in vitro,in animal models,and in human clinical trials.The antitumor effect of selective cyclooxygenase(COX)-2 inhibitors has been demonstrated in preclinical studies.However,no information is available on the effects of p53 gene therapy combined with selective COX-2 inhibitor on COX-2 gene expression and growth inhibition of human lung cancer cells.Methods We evaluated the effects of recombinant adenovirus-p53(Ad-p53) gene therapy combined with selective COX-2 inhibitor on the proliferation,apoptosis,cell cycle arrest of human lung adenocarcinoma A549 cell line,and the effects of tumor suppressor exogenous wild type p53 on COX-2 gene expression.ResultsAd-p53 gene therapy combined with selective COX-2 inhibitor celecoxib shows significant synergistic inhibition effects on the growth of human lung adenocarcinoma A549 cell line. Exogenous p53 gene can suppress COX-2 gene expression.ConclusionsSignificant synergistic inhibition effects of A549 cell line by the combined Ad-p53 and selective COX-2 inhibitor celecoxib may be achieved by enhancement of growth inhibition,apoptosis induction and suppression of COX-2 gene expression.This study provides first evidence that the administration of p53 gene therapy in combination with COX-2 inhibitors might be a new clinical strategy for the treatment or prevention of NSCLC.展开更多
AIM: To investigate the growth inhibitory mechanism of NS-398, a selective cyclooxygenase-2 (COX-2) inhibitor, in two hepatocellular carcinoma (HCC) cell lines (HepG2 and Huh7). METHODS: HepG2 and Huh7 cells were trea...AIM: To investigate the growth inhibitory mechanism of NS-398, a selective cyclooxygenase-2 (COX-2) inhibitor, in two hepatocellular carcinoma (HCC) cell lines (HepG2 and Huh7). METHODS: HepG2 and Huh7 cells were treated with NS-398. Its effects on cell viability, cell proliferation, cell cycles, and gene expression were respectively evaluated by water-soluble tetrazolium salt (WST-1) assay, 4’-6-diamidino-2-phenylindole (DAPI) staining, flow cytometer analysis, and Western blotting, with dimethyl sulfoxide (DMSO) as positive control. RESULTS: NS-398 showed dose- and time-dependent growth-inhibitory effects on the two cell lines. Proliferating cell nuclear antigen (PCNA) expressions in HepG2 and Huh7 cells, particularly in Huh7 cells were inhibited in a time- and dose-independent manner. NS-398 caused cell cycle arrest in the G1 phase with cell accumulation in the sub-G1 phase in HepG2 and Huh7 cell lines. No evidence of apoptosis was observed in two cell lines. CONCLUSION: NS-398 reduces cell proliferation by inducing cell cycle arrest in HepG2 and Huh7 cell lines, and COX-2 inhibitors may have potent chemoprevention effects on human hepatocellular carcinoma.展开更多
基金supported by Yunnan Provincial Science and Technology Department, No.2009CD079the National Natural Science Foundation ofChina, No.81060109.
文摘In this study, PC12 Adh cells and Neuro-2a cells were treated with Rho-associated kinase inhibitors （Y27632 and Fasudil）, a cyclooxygenase-1 selective inhibitor （SC560）, and a cyclooxygenase-2 inhibitor （NS398）. We found that these cells became tolerant to Rho-associated kinase inhibitors, as neurite outgrowth induced by these inhibitors diminished following more than 3 days of exposure in either cell line. The proteins cyclooxygenase-2 and cytosolic prostaglandin E synthetase were upregulated at day 3. NS398 decreased the tolerance to neurite outgrowth induction in both cell lines, whereas SC560 had almost no effect. These findings indicate that cells become tolerant to neurite outgrowth induced by Rho-associated kinase inhibitors, this is at least partly associated with upregulation of proteins involved in the cyclooxygenase-2 pathway, and cyclooxygenases-2 inhibition prevents this tolerance.
文摘AIM: To evaluate the opioid-sparing effect of selective cyclooxygenase-2(COX-2) inhibitors on short-term surgical outcomes after open colorectal surgery.METHODS: Patients undergoing open colorectal resection within an enhanced recovery after surgery protocol from 2011 to 2015 were reviewed. Patients with combined general anesthesia and epidural anesthesia, and those with acute colonic obstruction or perforation were excluded. Patients receiving selective COX-2 inhibitor were compared with well-matched individuals without such a drug. Outcome measures included numeric pain score and morphine milligram equivalent(MME) consumption on postoperative day(POD) 1-3, gastrointestinal recovery(time to tolerate solid diet and time to defecate), complications and length of postoperative stay.RESULTS: There were 75 patients in each group. Pain score on POD 1-3 was not significantly different between two groups. However, MME consumption and MME consumption per kilogram body weight on POD 1-3 was significantly less in patients receiving a selective COX-2 inhibitor(P < 0.001). Median MME consumption per kilogram body weight on POD 1-3 was 0.09, 0.06 and nil, respectively in patients receiving a selective COX-2 inhibitor and 0.22, 0.25 and 0.07, respectively in the comparative group(P < 0.001), representing at least 59% opioidreduction. Patients prescribing a selective COX-2 inhibitor had a shorter median time to resumption of solid diet [1(IQR 1-2) d vs 2(IQR 2-3) d; P < 0.001] and time to first defecation [2(IQR 2-3) d vs 3(IQR 3-4) d; P < 0.001]. There was no significant difference in overall postoperative complications between two groups. However, median postoperative stay was significantly 1-d shorter in patients prescribing a selective COX-2 inhibitor [4(IQR 3-5) d vs 5(IQR 4-6) d; P < 0.001]. CONCLUSION: Perioperative administration of oral selective COX-2 inhibitors significantly decreased intravenous opioid consumption, shortened time to gastrointestinal recovery and reduced hospital stay after open colorectal surgery.
文摘The discovery of COX-2 provides a novel target developing more effective NSAIDs with fewer side effects. On the basis of results from the structure-activity relationships (SAR) of selective COX-2 inhibitors, we have designed and synthesized some promising compounds.
文摘Background Gene therapy by adenovirus-mediated wild-type p53 gene transfer has been shown to inhibit lung cancer growth in vitro,in animal models,and in human clinical trials.The antitumor effect of selective cyclooxygenase(COX)-2 inhibitors has been demonstrated in preclinical studies.However,no information is available on the effects of p53 gene therapy combined with selective COX-2 inhibitor on COX-2 gene expression and growth inhibition of human lung cancer cells.Methods We evaluated the effects of recombinant adenovirus-p53(Ad-p53) gene therapy combined with selective COX-2 inhibitor on the proliferation,apoptosis,cell cycle arrest of human lung adenocarcinoma A549 cell line,and the effects of tumor suppressor exogenous wild type p53 on COX-2 gene expression.ResultsAd-p53 gene therapy combined with selective COX-2 inhibitor celecoxib shows significant synergistic inhibition effects on the growth of human lung adenocarcinoma A549 cell line. Exogenous p53 gene can suppress COX-2 gene expression.ConclusionsSignificant synergistic inhibition effects of A549 cell line by the combined Ad-p53 and selective COX-2 inhibitor celecoxib may be achieved by enhancement of growth inhibition,apoptosis induction and suppression of COX-2 gene expression.This study provides first evidence that the administration of p53 gene therapy in combination with COX-2 inhibitors might be a new clinical strategy for the treatment or prevention of NSCLC.
基金Supported by the Songeui Foundation of the Catholic University of Korea for Medical Research
文摘AIM: To investigate the growth inhibitory mechanism of NS-398, a selective cyclooxygenase-2 (COX-2) inhibitor, in two hepatocellular carcinoma (HCC) cell lines (HepG2 and Huh7). METHODS: HepG2 and Huh7 cells were treated with NS-398. Its effects on cell viability, cell proliferation, cell cycles, and gene expression were respectively evaluated by water-soluble tetrazolium salt (WST-1) assay, 4’-6-diamidino-2-phenylindole (DAPI) staining, flow cytometer analysis, and Western blotting, with dimethyl sulfoxide (DMSO) as positive control. RESULTS: NS-398 showed dose- and time-dependent growth-inhibitory effects on the two cell lines. Proliferating cell nuclear antigen (PCNA) expressions in HepG2 and Huh7 cells, particularly in Huh7 cells were inhibited in a time- and dose-independent manner. NS-398 caused cell cycle arrest in the G1 phase with cell accumulation in the sub-G1 phase in HepG2 and Huh7 cell lines. No evidence of apoptosis was observed in two cell lines. CONCLUSION: NS-398 reduces cell proliferation by inducing cell cycle arrest in HepG2 and Huh7 cell lines, and COX-2 inhibitors may have potent chemoprevention effects on human hepatocellular carcinoma.
