Background Lumiracoxib is a highly selective cyclooxygenase-2 （COX-2） inhibitor with antiinflammatory, analgesic and antipyretic activities comparable with class specific drugs, but with much improved gastrointestin...Background Lumiracoxib is a highly selective cyclooxygenase-2 （COX-2） inhibitor with antiinflammatory, analgesic and antipyretic activities comparable with class specific drugs, but with much improved gastrointestinal safety. No studies have examined lumiracoxib for antitumorigenic activity on human nonsmall cell lung cancer cell lines in vitro or its possible molecular mechanisms. Methods The antiproliferative effect of lumiracoxib alone or combined with docetaxol on A549 and NCI-H460 lines was assessed by 3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyltetrazolium bromide （MTT） assay. Drug-drug interactions were analyzed using the coefficient of drug interaction （CDI） to characterize the interactions as synergism, additivity or antagonism. Morphological changes were observed by acridine orange fluorescent staining. Extent of apoptosis was determined by flow cytometry. Results Lumiracoxib （15-240 pmol/L） has an inhibitory effect on the proliferation of A549 and NCI-H460 cell lines in concentration- and time-dependent manners with the ICso values of 2597 pmol/L and 833 pmol/L, respectively. The synergistic effect was prominent when lumiracoxib （15-240 pmoVL） was combined with docetaxol （0.2-2 pmol/L） （CDI 〈1）. Fluorescent staining showed that lumiracoxib could induce apoptosis in A549 and NCI-H460 cells. Lumiracoxib treatment also caused an increase of the sub-G1 fraction in each cell line and resulted in an increase of G0/Gl-phase cells and a decrease of S-phase cells. Conclusions Lumiracoxib had antiproliferative effect on the human nonsmall cell lung cancer cell lines A549 and NCI-H460 and had a significant synergy with docetaxol, which may be related to apoptotic induction and cell cycle arrest.展开更多
Background Tenidap is a liposoluble non-steroidal anti-inflammatory drug that is easily distributed in the central nervous system and also inhibits the production and activity of cyclooxygenase-2 （COX-2） and cytokin...Background Tenidap is a liposoluble non-steroidal anti-inflammatory drug that is easily distributed in the central nervous system and also inhibits the production and activity of cyclooxygenase-2 （COX-2） and cytokines in vitro. This study aimed to evaluate the neuroprotective effect of tenidap in a pilocarpine rat model of temporal lobe epilepsy （TLE）. Methods Tenidap was administered daily at 10 mg/kg for 10 days following pilocarpine-induced status epilepticus （SE） in male Wistar rats after which prolonged generalized seizures resulted in TLE. After tenidap treatment, spontaneous recurrent seizures （SRSs） were recorded by video monitoring （for 7 hours per day for 14 days）. The frequency and severity of the SRSs were observed. Histological and immunocytochemical analyses were used to evaluate the neuroprotective effect of tenidap and detect COX-2 expression, which may be associated with neuronal death. Results There were 46.88±10.70 survival neurons in tenidap-SE group, while there were 27.60±5.18 survival neurons in saline-SE group at -2.4 mm field in the CA3 area. There were 37.75±8.78 survival neurons in tenidap-SE group, while there were 33.40±8.14 survival neurons in saline-SE group at -2.4 mm field in the CA1 area. Tenidap treatment significantly reduced neuronal damage in the CA3 area （P 〈0.05） and slightly reduced damage in the CA1 area. Tenidap markedly inhibited COX-2 expression in the hippocampus, especially in the CA3 area. Conclusion Tenidap conferred neuroprotection to the CA3 area in a pilocarpine-induced rat model of TLE by inhibiting COX-2 expression.展开更多
基金This work was supported by grants from the Natural Science Foundation of Anhui Province （No. 07021008） and the General Project of the Natural Science Foundation of the Department of Education, Anhui Province （No. KJ2007B142）.
文摘Background Lumiracoxib is a highly selective cyclooxygenase-2 （COX-2） inhibitor with antiinflammatory, analgesic and antipyretic activities comparable with class specific drugs, but with much improved gastrointestinal safety. No studies have examined lumiracoxib for antitumorigenic activity on human nonsmall cell lung cancer cell lines in vitro or its possible molecular mechanisms. Methods The antiproliferative effect of lumiracoxib alone or combined with docetaxol on A549 and NCI-H460 lines was assessed by 3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyltetrazolium bromide （MTT） assay. Drug-drug interactions were analyzed using the coefficient of drug interaction （CDI） to characterize the interactions as synergism, additivity or antagonism. Morphological changes were observed by acridine orange fluorescent staining. Extent of apoptosis was determined by flow cytometry. Results Lumiracoxib （15-240 pmol/L） has an inhibitory effect on the proliferation of A549 and NCI-H460 cell lines in concentration- and time-dependent manners with the ICso values of 2597 pmol/L and 833 pmol/L, respectively. The synergistic effect was prominent when lumiracoxib （15-240 pmoVL） was combined with docetaxol （0.2-2 pmol/L） （CDI 〈1）. Fluorescent staining showed that lumiracoxib could induce apoptosis in A549 and NCI-H460 cells. Lumiracoxib treatment also caused an increase of the sub-G1 fraction in each cell line and resulted in an increase of G0/Gl-phase cells and a decrease of S-phase cells. Conclusions Lumiracoxib had antiproliferative effect on the human nonsmall cell lung cancer cell lines A549 and NCI-H460 and had a significant synergy with docetaxol, which may be related to apoptotic induction and cell cycle arrest.
基金This study was supported by a grant of National Natural Science Foundation of China （No. 81100964）.
文摘Background Tenidap is a liposoluble non-steroidal anti-inflammatory drug that is easily distributed in the central nervous system and also inhibits the production and activity of cyclooxygenase-2 （COX-2） and cytokines in vitro. This study aimed to evaluate the neuroprotective effect of tenidap in a pilocarpine rat model of temporal lobe epilepsy （TLE）. Methods Tenidap was administered daily at 10 mg/kg for 10 days following pilocarpine-induced status epilepticus （SE） in male Wistar rats after which prolonged generalized seizures resulted in TLE. After tenidap treatment, spontaneous recurrent seizures （SRSs） were recorded by video monitoring （for 7 hours per day for 14 days）. The frequency and severity of the SRSs were observed. Histological and immunocytochemical analyses were used to evaluate the neuroprotective effect of tenidap and detect COX-2 expression, which may be associated with neuronal death. Results There were 46.88±10.70 survival neurons in tenidap-SE group, while there were 27.60±5.18 survival neurons in saline-SE group at -2.4 mm field in the CA3 area. There were 37.75±8.78 survival neurons in tenidap-SE group, while there were 33.40±8.14 survival neurons in saline-SE group at -2.4 mm field in the CA1 area. Tenidap treatment significantly reduced neuronal damage in the CA3 area （P 〈0.05） and slightly reduced damage in the CA1 area. Tenidap markedly inhibited COX-2 expression in the hippocampus, especially in the CA3 area. Conclusion Tenidap conferred neuroprotection to the CA3 area in a pilocarpine-induced rat model of TLE by inhibiting COX-2 expression.
