摘要目的 研究蛋白磷酸酶2A(PP2A)抑制剂对胰腺癌细胞系PANC-1活力的影响及其机制.方法 用PP2A抑制剂斑蝥素和冈田酸处理PANC-1细胞.通过Western印迹检测核因子(NF) -κB通路的激活程度.通过转染PP2A活性亚基cα(PP2A cα)表达质粒、NF-κB抑制蛋白激酶(IKK)α和NF-κB抑制蛋白(IκB)α的显性负性突变体、p65干扰质粒,分别从各环节阻断NF-κB通路,通过四甲基偶氮唑盐比色法(MTT法)检测细胞活力.结果 PP2A抑制剂可使IKKa磷酸化,进一步使IκBa磷酸化并降解,继而释放p65入核.过表达PP2Acα、IKKα显性负性突变体、IκBα显性负性突变体或干扰p65可分别使斑蝥素对细胞活力的抑制率下降(31.85±13.37)％、(23.48±8.98)％、(22.63±5.81)％、(20.88±3.24)％,使冈田酸对细胞活力的抑制率下降(40.17±11.65)％、(27.34±14.28)％、(24.85±3.39)％、(27.08±3.81)％.结论 PP2A抑制剂通过PP2A/IKKα/IκBα/p65依赖性通路发挥抗胰腺癌作用.

abstractsObjective To investigate the effects of protein phosphatase 2A (PP2A) inhibitors on the viability of pancreatic cancer cell line PANC-1 and its mechanism.Methods PANC-1 cells were treated with PP2A inhibitors Cantharidin or Okadiac acid.The activity degree of NF-κB pathway was tested by Western blot.NF-κB pathway was blocked from all sectors by PP2Acα plamid transfection,NF-κB inhibition of protein kinase α (IKKα) and NF-κB inhibitor α (IκBα) dominant negative mutant and p65 interfering plasmid.Cell viability was determined by MTT.Results PP2A inhibitors could induce phosphorylation of IKKα,further phosphorylation of IκBα and degradation and followed by the release of p65 into nucleus.When PP2Acα,IKKα dominant negative mutant and IκBα dominant negative mutant were overexpressed,or p65 was interfered,the inhibition rate of Cantharidin on cell viability decreased (31.85±13.37) ％,(23.48±8.98)％,(22.63±5.81)％ and (20.88±3.24)％respectively,and the inhibition rate of Okadiac acid on cell viability decreased (40.17 ± 11.65)％,(27.34±14.28)％,(24.85±3.39)％ and (27.08±3.81)％ respectively.Conclusions PP2Ainhibitors play a role in preventing pancreatic cancer through PP2Acα/IKKα/IκBα/p65 pathway.