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目的 :探讨选择性环氧合酶2(cyclooxygenase-2,COX-2)抑制剂塞来昔布对人急性单核细胞白血病细胞增殖和凋亡的影响。方法 :不同浓度的塞来昔布处理THP-1细胞后,应用MTS法检测THP-1细胞的增殖情况,FCM法检测细胞凋亡和细胞周期,蛋白质印迹法检测caspase-3剪切片段(cleaved-caspase-3)、聚腺苷二磷酸核糖聚合酶1剪切片段(cleaved poly ADP-ribose polymerase-1,cleaved-PARP-1)、核因子κB抑制剂激酶(βinhibitor of nuclear factor kappa B kinaseβ,IKKβ)、磷酸化IKKβ(phospho-IKKβ,p-IKKβ)、丝氨酸-苏氨酸蛋白激酶(seride-threonine protein kinase,又称Akt)、磷酸化Akt(phospho-Akt,p-Akt)和survivin蛋白的表达。结果 :不同浓度的塞来昔布均可抑制THP-1细胞的增殖,诱导THP-1细胞的凋亡,并将细胞阻滞于G0/G1期(P值均<0.05)。不同浓度的塞来昔布处理后,THP-1细胞中p-Akt、p-IKKβ和survivin蛋白的表达水平均显著下调(P值均<0.05);当塞来昔布的浓度大于6μmol/L时,THP-1细胞中cleaved-caspase-3和cleaved-PARP蛋白的表达水平均显著上调(P值均<0.05)。结论 :塞来昔布能抑制THP-1细胞的增殖并诱导细胞凋亡,这一作用可能与Akt/核因子κB(nuclear factor kappa B,NF-κB)信号通路及抗凋亡蛋白survivin的表达有关。
Objective: To investigate the effect of selective cyclooxygenase-2 (COX-2) inhibitor celecoxib on the proliferation and apoptosis of human acute monocytic leukemia cells. Methods: THP-1 cells were treated with different concentrations of celecoxib, the proliferation of THP-1 cells was detected by MTS assay, the apoptosis and cell cycle were detected by FCM, and the cleaved -caspase-3), cleaved poly ADP-ribose polymerase-1 (cleaved-PARP-1), β-inhibitor of nuclear factor kappa B kinaseβ IKKβ), phospho-IKKβ (p-IKKβ), seride-threonine protein kinase (AKT), phospho- Akt (p-Akt) and survivin protein expression. RESULTS: Celecoxib could inhibit the proliferation of THP-1 cells and induce the apoptosis of THP-1 cells. The cells were arrested in G0 / G1 phase (all P <0.05). The expression of p-Akt, p-IKKβ and survivin in THP-1 cells were significantly down-regulated after treated with different concentrations of celecoxib (P <0.05). When the concentration of celecoxib was higher than 6 μmol / L , The expression of cleaved-caspase-3 and cleaved-PARP in THP-1 cells were significantly up-regulated (P <0.05). CONCLUSION: Celecoxib inhibits the proliferation and induces apoptosis of THP-1 cells, which may be related to the expression of NF-κB signal pathway and survivin of Akt / NF-κB related.