AIM： To investigate the cyclooxygenase-2 （COX-2） expression level in human HepG2, Bel-7402 and SMMC-7721 hepatoma cell lines and the molecular mechanism of COX-2 selective inhibitor celecoxib-induced cell growth in...AIM： To investigate the cyclooxygenase-2 （COX-2） expression level in human HepG2, Bel-7402 and SMMC-7721 hepatoma cell lines and the molecular mechanism of COX-2 selective inhibitor celecoxib-induced cell growth inhibition and cell apoptosis. METHODS： Hepatoma cells were cultured and treated with celecoxib. Cell in situ hybridization （ISH） and immunocytochemistry were used to detect COX-2 mRNA and protein expression. Proliferating cell nuclear antigen and phosphorylated Akt were also detected by immunocytochemistry assay. Cell growth rates were assessed by 3-（4, 5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium （MTT） bromide colorimetric assay. Celecoxib- induced cell apoptosis was measured by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL） and flow cytometry （FCM）. The phosphorylated Akt and activated fragments of caspase-9, caspase-3 were examined by Western blotting analysis. RESULTS： Increased COX-2 mRNA and protein expression were detected in all three hepatoma cell lines. Celecoxib could significantly inhibit cell growth and the inhibitory effect was in a dose- and time-dependent manner evidenced by MTT assays and morphological changes. The apoptotic index measured by TUNEL increased correspondingly with the increased concentration of celecoxib and the reaction time. With 50 μmol/L celecoxib treatment for 24 h, the apoptotic index of HepG2, BEL-7402 and SMMC-7721 cells was 25.01±3.08%, 26.40±3.05%,and 30.60±2.89%, respectively. Western blotting analysis showed remarkable activation of caspase-9, caspase-3 and dephosphorylation of Akt （Thr^308）. Immunocytochemistry also showed the reduction of PCNA expression and phosphorylation Akt （Thr^308） after treatment with celecoxib. CONCLUSION： COX-2 mRNA and protein overexpression in HepG2, Bel-7402 and SMMC-7721 cell lines correlate with the increased cell growth rate. Celecoxib can inhibit proliferation and induce apoptosis of hepatoma cell strains in a dose- and time-dependent manner.展开更多
Phenyl sulfone-containing 2, 3-diarylindole derivatives were designed and identified to be selective COX-2 inhibitors. A convenient synthetic route was also developed for the synthesis of the novel inhibitors.
Objectives: Osteoarthritis (OA) has a dramatic impact on patients’ health related quality of life (HRQoL). Chronic use of analgesics and anti-inflammatory medications for pain management may improve symptoms but on l...Objectives: Osteoarthritis (OA) has a dramatic impact on patients’ health related quality of life (HRQoL). Chronic use of analgesics and anti-inflammatory medications for pain management may improve symptoms but on long term may affect HRQoL negatively. The objective of the present study was to compare the impact of two different classes of analgesics, traditional non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclo-oxygenase-2 (COX-2) inhibitors on HRQoL among osteoarthritis patients using the SF-36 questionnaire. Methods: Clinic based cross-sectional study conducted at Al-Qassimi Hospital, Sharjah, United Arab Emirates (UAE), over a period of six months. Ethical Approval was obtained from the ethics committee at Al-Qassimi Clinical Research Center. Total of 200 osteoarthritis patients fulfilling the inclusion and exclusion criteria were involved in the study. Patients’ demographics were collected from their medical records. The Medical Outcome Study Short-Form 36 (SF-36) questionnaire was used to measure patients’ HRQoL. SF-36 data were scored using health outcomes scoring software 4.5. Results: Mean age of the subjects was 62.19 ± 9.81 years with females constituting 151 (75.5%) of the patients. In general, females scored lower in most of the HRQoL domains compared to males and there was significant difference between the two groups in the mental health (p = 0.005) & mental component (p = 0.042) domains. Compared to selective COX-2 inhibitors, patients on NSAIDs scored higher on all domains of SF-36 except physical functioning. There was significant difference in mental health domain for patients treated with NSAIDs (p = 0.02). Celecoxib was only better than NSAIDs in osteoarthritis patients with more than one musculoskeletal disorders in the domain of bodily pain (p = 0.009). Conclusion: NSAIDs-treated patients did not differ significantly from celecoxib-treated patients in all domains of the SF-36 except for the mental health domain.展开更多
基金Supported by Medical Science Research Foundation of Jiangsu Health Bureau Grant Z200314 (to JL)Medical Science Research Foundation of Nanjing Medical University Grant NY1999023 (to NBL) and CX2003012 (to JL)
文摘AIM： To investigate the cyclooxygenase-2 （COX-2） expression level in human HepG2, Bel-7402 and SMMC-7721 hepatoma cell lines and the molecular mechanism of COX-2 selective inhibitor celecoxib-induced cell growth inhibition and cell apoptosis. METHODS： Hepatoma cells were cultured and treated with celecoxib. Cell in situ hybridization （ISH） and immunocytochemistry were used to detect COX-2 mRNA and protein expression. Proliferating cell nuclear antigen and phosphorylated Akt were also detected by immunocytochemistry assay. Cell growth rates were assessed by 3-（4, 5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium （MTT） bromide colorimetric assay. Celecoxib- induced cell apoptosis was measured by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL） and flow cytometry （FCM）. The phosphorylated Akt and activated fragments of caspase-9, caspase-3 were examined by Western blotting analysis. RESULTS： Increased COX-2 mRNA and protein expression were detected in all three hepatoma cell lines. Celecoxib could significantly inhibit cell growth and the inhibitory effect was in a dose- and time-dependent manner evidenced by MTT assays and morphological changes. The apoptotic index measured by TUNEL increased correspondingly with the increased concentration of celecoxib and the reaction time. With 50 μmol/L celecoxib treatment for 24 h, the apoptotic index of HepG2, BEL-7402 and SMMC-7721 cells was 25.01±3.08%, 26.40±3.05%,and 30.60±2.89%, respectively. Western blotting analysis showed remarkable activation of caspase-9, caspase-3 and dephosphorylation of Akt （Thr^308）. Immunocytochemistry also showed the reduction of PCNA expression and phosphorylation Akt （Thr^308） after treatment with celecoxib. CONCLUSION： COX-2 mRNA and protein overexpression in HepG2, Bel-7402 and SMMC-7721 cell lines correlate with the increased cell growth rate. Celecoxib can inhibit proliferation and induce apoptosis of hepatoma cell strains in a dose- and time-dependent manner.
基金support for this study was provided by the National Natural Science foundation of China.
文摘Phenyl sulfone-containing 2, 3-diarylindole derivatives were designed and identified to be selective COX-2 inhibitors. A convenient synthetic route was also developed for the synthesis of the novel inhibitors.
文摘Objectives: Osteoarthritis (OA) has a dramatic impact on patients’ health related quality of life (HRQoL). Chronic use of analgesics and anti-inflammatory medications for pain management may improve symptoms but on long term may affect HRQoL negatively. The objective of the present study was to compare the impact of two different classes of analgesics, traditional non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclo-oxygenase-2 (COX-2) inhibitors on HRQoL among osteoarthritis patients using the SF-36 questionnaire. Methods: Clinic based cross-sectional study conducted at Al-Qassimi Hospital, Sharjah, United Arab Emirates (UAE), over a period of six months. Ethical Approval was obtained from the ethics committee at Al-Qassimi Clinical Research Center. Total of 200 osteoarthritis patients fulfilling the inclusion and exclusion criteria were involved in the study. Patients’ demographics were collected from their medical records. The Medical Outcome Study Short-Form 36 (SF-36) questionnaire was used to measure patients’ HRQoL. SF-36 data were scored using health outcomes scoring software 4.5. Results: Mean age of the subjects was 62.19 ± 9.81 years with females constituting 151 (75.5%) of the patients. In general, females scored lower in most of the HRQoL domains compared to males and there was significant difference between the two groups in the mental health (p = 0.005) & mental component (p = 0.042) domains. Compared to selective COX-2 inhibitors, patients on NSAIDs scored higher on all domains of SF-36 except physical functioning. There was significant difference in mental health domain for patients treated with NSAIDs (p = 0.02). Celecoxib was only better than NSAIDs in osteoarthritis patients with more than one musculoskeletal disorders in the domain of bodily pain (p = 0.009). Conclusion: NSAIDs-treated patients did not differ significantly from celecoxib-treated patients in all domains of the SF-36 except for the mental health domain.
