塞来昔布促进人急性单核细胞白血病THP-1细胞凋亡

Celecoxib promots the apoptosis of acute monocytic leukemia THP-1 cell line

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 inhibitor celecoxib on the myeloid leukemia cells. effects of cyclooxygenase-2 （COX-2） proliferation and apoptosis of acute Methods： After acute monocytic leukemia cell line THP-1 treatment with different concentrations of celecoxib, the proliferation, apoptosis and cell cycle distribution of THP-1 cells were detected by MTS and FCM, respectively. The expressions of cleaved-caspase-3, cleaved poly ADP-ribose polymerase-1 （cleaved-PARP-1）, inhibitor of nuclear factor kappa-B kinase 13 （IKK13）, phospho- IKKI3 （p-IKKI3）, seride-threonine protein kinase （Akt）, phospho-Akt （p-Akt） and survivin proteins in THP-1 cells were detected after treatment with different concentrations of celecoxib. Results： Different concentrations of celecoxib inhibited the proliferation of THP-1 cells, induced the apoptosis of THP-1 cells, and arrested the cell cycles of THP-1 cells at G0/G1 phase （all P 〈 0.05）. The expression levels of p-Akt, p-IKKI3 and survivin proteins in THP-1 cells after treatment with different concentrations of celecoxib were significantly down- regulated （all P 〈 0.05）, while the expression levels of cleaved-caspase-3 and cleaved- PARP-1 in THP-1 cells after treatment with celecoxib （〉 6 μmol/L） were significantly upregulated （all P 〈 0.05）. Conclusion： Celecoxib can inhibit the proliferation and induce the apoptosis of THP-1.This effect may be related to Akt/nuclear factor kappa B （NF-KB） signaling pathway and the expression of anti-apoptotic protein survivin.