蛋白磷酸酶2A抑制剂对胰腺癌细胞活力的影响及其机制  

The effects of protein phosphatase 2A inhibitors on the viability of pancreatic cancer cell and its mechanism

作　　者：李伟[1] 陈政[1] 龚斐然[2] 宗洋[1] 苗毅[1] 陶敏[3] 徐泽宽[1] 

机构地区：[1]南京医科大学第一附属医院普外科,,210029 [2]苏州大学附属第一医院血液科 [3]苏州大学附属第一医院肿瘤科

出　　处：《中华消化杂志》2012年第1期42-45,共4页Chinese Journal of Digestion

基　　金：国家自然科学基金（81072031、81101867）;江苏省自然科学基金（BK2010585）;苏州市科教兴卫青年科技项目（SWKQ1003,SWKQ1011）

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ca（PP2Aca）表达质粒、NF-κB抑制蛋白激酶（IKK）a和NF-κB抑制蛋白（IκB）a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IKBa磷酸化并降解，继而释放p65入核。过表达PP2Aca、IKKa显性负性突变体、IKBa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士14．28）％、（24．85±3．39）％、（27．08±3．81）％。结论PP2A抑制剂通过PP2A／IKKa／IκBa／p65依赖性通路发挥抗胰腺癌作用。Objective To investigate the effects of protein phosphatase 2A （PP2A） inhibitors on the viability of pancreatic cancer cell line PANC-1 and its mechanisrrl. 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 PP2Aca plamid transfection, NF-κB inhibition of protein kinase a （IKKa） and NF-κB inhibitor a （IκBa） dominant negative mutant and p65 interfering plasmid. Cell viability was determined by MTT. Results PP2A inhibitors could induce phosphorylation of IKKa, further phosphorylation of IκBa and degradation and followed by the release of p65 into nucleus. When PP2Aca, IKKa dominant negative mutant and IκBa 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. 8]）% respectively. Conclusions PP2A inhibitors play a role in preventing pancreatic cancer through PP2Aca/IKKa/IKBa/p65 pathway.

关 键 词：胰腺肿瘤 蛋白质磷酸酶2 斑蝥素 冈田酸 核因子-ΚB 磷酰化 

分 类 号：R735.9[医药卫生—肿瘤]