中华消化杂志
中華消化雜誌
중화소화잡지
Chinese Journal of Digestion
2012年
1期
42-45
,共4页
李伟%陈政%龚斐然%宗洋%苗毅%陶敏%徐泽宽
李偉%陳政%龔斐然%宗洋%苗毅%陶敏%徐澤寬
리위%진정%공비연%종양%묘의%도민%서택관
胰腺肿瘤%蛋白质磷酸酶2%斑蝥素%冈田酸%核因子-κB%磷酰化
胰腺腫瘤%蛋白質燐痠酶2%斑蝥素%岡田痠%覈因子-κB%燐酰化
이선종류%단백질린산매2%반모소%강전산%핵인자-κB%린선화
Pancreatic neoplasms%Protein phosphatase 2%Cantharidin%Okadiac acid%NFkappa B%Phosphorylation
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.
目的 研究蛋白燐痠酶2A(PP2A)抑製劑對胰腺癌細胞繫PANC-1活力的影響及其機製.方法 用PP2A抑製劑斑蝥素和岡田痠處理PANC-1細胞.通過Western印跡檢測覈因子(NF) -κB通路的激活程度.通過轉染PP2A活性亞基cα(PP2A cα)錶達質粒、NF-κB抑製蛋白激酶(IKK)α和NF-κB抑製蛋白(IκB)α的顯性負性突變體、p65榦擾質粒,分彆從各環節阻斷NF-κB通路,通過四甲基偶氮唑鹽比色法(MTT法)檢測細胞活力.結果 PP2A抑製劑可使IKKa燐痠化,進一步使IκBa燐痠化併降解,繼而釋放p65入覈.過錶達PP2Acα、IKKα顯性負性突變體、IκBα顯性負性突變體或榦擾p65可分彆使斑蝥素對細胞活力的抑製率下降(31.85±13.37)％、(23.48±8.98)％、(22.63±5.81)％、(20.88±3.24)％,使岡田痠對細胞活力的抑製率下降(40.17±11.65)％、(27.34±14.28)％、(24.85±3.39)％、(27.08±3.81)％.結論 PP2A抑製劑通過PP2A/IKKα/IκBα/p65依賴性通路髮揮抗胰腺癌作用.
목적 연구단백린산매2A(PP2A)억제제대이선암세포계PANC-1활력적영향급기궤제.방법 용PP2A억제제반모소화강전산처리PANC-1세포.통과Western인적검측핵인자(NF) -κB통로적격활정도.통과전염PP2A활성아기cα(PP2A cα)표체질립、NF-κB억제단백격매(IKK)α화NF-κB억제단백(IκB)α적현성부성돌변체、p65간우질립,분별종각배절조단NF-κB통로,통과사갑기우담서염비색법(MTT법)검측세포활력.결과 PP2A억제제가사IKKa린산화,진일보사IκBa린산화병강해,계이석방p65입핵.과표체PP2Acα、IKKα현성부성돌변체、IκBα현성부성돌변체혹간우p65가분별사반모소대세포활력적억제솔하강(31.85±13.37)％、(23.48±8.98)％、(22.63±5.81)％、(20.88±3.24)％,사강전산대세포활력적억제솔하강(40.17±11.65)％、(27.34±14.28)％、(24.85±3.39)％、(27.08±3.81)％.결론 PP2A억제제통과PP2A/IKKα/IκBα/p65의뢰성통로발휘항이선암작용.
Objective 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.
