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gamma-Secretase inhibitor DAPT sensitizes t-AUCB-induced apoptosis of human glioblastoma cells in vitro via blocking the p38 MAPK/MAPKAPK2/Hsp27 pathway

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收录情况: ◇ SCIE ◇ 统计源期刊 ◇ CSCD-C

机构: [1]Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China [2]Department of Neurosurgery, Second Affiliated Hospital of Soochow University, Suzhou 215004, China
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关键词: glioma chemotherapy gamma-secretase DAPT soluble epoxide hydrolase t-AUCB apoptosis caspase-3 p38 MAPK MAPKAPK2 Hsp27

摘要:
Aim: Trans-444-(3-adamantan-1-yl-ureido)-cyalohexyloxy]-benzoic acid (t-AUCB) is a soluble epoxide hydrolase inhibitor that suppresses glioblastoma cell growth in vitro. The aim of this study was to examine whether the y-secretase inhibitor ARN-(3,5-difluorophenacety1)-1alanyl]-S-phenylglycine t-butyl ester (DAPT) could sensitize glioma cells to t-AUCB-induced apoptosis. Methods: Both U251 and U87 human glioblastoma cell lines were tested. Cell growth was assessed using the cell counting kit-8. Cell apoptosis was detected with caspase-3 activity assay kits and flow cytometry. The protein levels in the p38 MAPK/MAPKAPK2/Hsp27 pathway in the cells were analyzed using Western blots. Results: Pretreatment with DAPT (2 mu mol/L) substantially potentiated the growth inhibition caused by t-AUCB (200 pmol/L) in U251 and U87 cells. Furthermore, pretreatment with DAPT markedly increased t-AUCB-induced apoptosis of U251 and U87 cells. T-AUCB alone did not significant affect caspase-3 activity in the cells, but t-AUCB plus DAPT pretreatment caused significant increase of caspase-3 actiyity. Furthermore, pretreatment with DAPT completely blocked t-AUCB-induced phosphorylation of p38 MAPK, MAPKAPK2 and Hsp27 in the cells. Conclusion: The y-secretase inhibitor DAPT sensitizes t-AUCB-induced apoptosis of human glioblastoma cells in vitro via blocking the p38 MAPK/MAPKAPK2/Hsp27 pathway, suggesting that the combination of t-AUCB and DAPT may be a potentially effective strategy for the treatment of glioblastoma.

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出版当年[2013]版:
大类 | 4 区 医学
小类 | 4 区 化学综合 4 区 药学
最新[2023]版:
大类 | 1 区 医学
小类 | 1 区 药学 2 区 化学:综合
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出版当年[2012]版:
Q2 CHEMISTRY, MULTIDISCIPLINARY Q2 PHARMACOLOGY & PHARMACY
最新[2023]版:
Q1 CHEMISTRY, MULTIDISCIPLINARY Q1 PHARMACOLOGY & PHARMACY

影响因子: 最新[2023版] 最新五年平均 出版当年[2012版] 出版当年五年平均 出版前一年[2011版] 出版后一年[2013版]

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第一作者机构: [1]Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China
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通讯机构: [1]Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China
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