The effects of protein phosphatase 2A inhibitors on the viability of pancreatic cancer cell and its mechanism
10.3760/cma.j.issn.0254-1432.2012.01.010
- VernacularTitle:蛋白磷酸酶2A抑制剂对胰腺癌细胞活力的影响及其机制
- Author:
Wei LI
;
Zheng CHEN
;
Feiran GONG
;
Yang ZONG
;
Yi MIAO
;
Min TAO
;
Zekuan XU
- Publication Type:Journal Article
- Keywords:
Pancreatic neoplasms;
Protein phosphatase 2;
Cantharidin;
Okadiac acid;
NFkappa B;
Phosphorylation
- From:
Chinese Journal of Digestion
2012;32(1):42-45
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effects of protein phosphatase 2A (PP2A) inhibitors on the viability of pancreatic cancer cell line PANC-1 and its mechanism.MethodsPANC-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.ResultsPP2A 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.ConclusionsPP2Ainhibitors play a role in preventing pancreatic cancer through PP2Acα/IKKα/IκBα/p65 pathway.