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    三氧化二砷对恶性黑素瘤A375细胞NF-κB、C-IAP2及caspase-3表达的影响

    The effect of As2O3 on expressions of NF-κB,C-IAP2 and caspase-3 in melanoma A375 cell lines

      摘要
    • 摘要: 目的:探讨三氧化二砷(arsenic trioxide,As2O3)在诱导人黑素瘤A375细胞凋亡中,对核因子-κB(NF-κB)、细胞凋亡抑制蛋白2(C-IAP2)以及半胱氨酸-天冬氨酸特异性蛋白酶-3(caspase-3)表达的影响。方法:Western blot法检测A375细胞中NF-κB p65核蛋白的表达和caspase-3蛋白的活化,半定量RT-PCR法检测C-IAP2mRNA的表达。结果:2.5、5.0、10.0μmol/LAs2O3作用于A375细胞24h,NF-κB p65核蛋白表达比值分别为(39.60±7.76)%、(10.17±0.90)%和(4.43±0.91)%;caspase-3蛋白比值分别为(10.03±2.06)%、(23.43±3.28)%和(35.70±4.61)%;C-IAP2mRNA表达的比值为(66.78±15.46)%、(30.16±5.52)%和(6.46±4.54)%,上述各指标与相应对照组比较及组内两两比较差异均有统计学意义(P<0.05~P<0.01),随着As2O3作用浓度的增加,caspase-3激活型蛋白增多,NF-κB p65核蛋白和C-IAP2mRNA表达下降。结论:As2O3能抑制NF-κB、C-IAP2基因的表达,活化caspase-3蛋白表达。推测NF-κB-C-IAP2-caspase-3通路可能是As2O3诱导A375细胞凋亡的途径之一。

       

      Abstract: Objective: To explore the effect of As2O3 on expressions of NF-κB,C-IAP2 and caspase-3 in melanoma A375 cell line.Methods: The expression of NF-κB p65 nuclear protein and the activity of caspase-3 were examined by Western blot,the expression of C-IAP2 mRNA was examined by semi-quantitative RT-PCR in A375 cells.Results: Treated with 2.5,5.0 and 10.0 μmol/L As2O3 for 24 h,the expression ratio of NF-κB p65 nucleoprotein was(39.60±7.76)%,(10.17±0.90)% and(4.43±0.91)%,respectively;the expression ratio of cleaved caspase-3 was(10.03±2.06)%,(23.43±3.28)% and(35.70±4.61)%,respectively;the ratio of C-IAP2 mRNA was(66.78±15.46)%,(30.16±5.52)% and(6.46±4.54)%,respectively.There was significant difference between control group and experiment group(P<0.05 to P<0.01) (P<0.01).With the concentration of As2O3 increasing,caspase-3 was activated dramatically,NF-κB p65 and C-IAP2 mRNA decreased dramatically.Conclusions: The signal transduction pathway of NF-κB,C-IAP2 and caspase-3 may be associated the apoptosis of A375 cells induced by As2O3.

       

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