PP2A inhibitors induce apoptosis in pancreatic cancer cell line PANC-1 through persistent phosphorylation of IKKα and sustained activation of the NF-κB pathway

被引：50

作者：

Li, Wei ^{[1
,2
,3
]}

Chen, Zheng ^{[1
]}

Zong, Yang ^{[1
]}

Gong, Feiran ^{[2
]}

Zhu, Yi ^{[1
]}

Zhu, Yunxia ^{[2
]}

Lv, Jinghuan ^{[2
]}

Zhang, Jingjing ^{[1
]}

Xie, Li ^{[1
]}

Sun, Yujie ^{[2
,4
]}

Miao, Yi ^{[1
,4
]}

Tao, Min ^{[3
]}

Han, Xiao ^{[1
,2
]}

Xu, Zekuan ^{[1
,4
]}

机构：

[1] Nanjing Med Univ, Dept Gen Surg, Affiliated Hosp 1, Nanjing 210029, Peoples R China

[2] Nanjing Med Univ, Key Lab Human Funct Genom Jiangsu Prov, Nanjing 210029, Peoples R China

[3] Soochow Univ, Dept Oncol, Affiliated Hosp 1, Suzhou 215006, Peoples R China

[4] Nanjing Med Univ, Ctr Canc, Nanjing 210029, Peoples R China

来源：

CANCER LETTERS | 2011年 / 304卷 / 02期

基金：

中国国家自然科学基金;

关键词：

PP2A; Pancreatic cancer; Apoptosis; IKK alpha; NF-kappa B; PROTEIN PHOSPHATASE 2A; TRAIL-INDUCED APOPTOSIS; GENE-EXPRESSION; KINASE ACTIVATION; OKADAIC ACID; CANTHARIDIN; NORCANTHARIDIN; THERAPY; DEATH; PROGRESSION;

D O I：

10.1016/j.canlet.2011.02.009

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Serine/threonine protein phosphatase 2A (PP2A), is thought to be a cancer suppresser, as inhibition of PP2A can induce phosphorylation and activation of substrate kinases, most of which can accelerate growth. Interestingly, cantharidin potently inhibits PP2A but efficiently represses various cancer cells. In the present study, we found that PP2A inhibitors, cantharidin or Okadaic acid, inhibited cell viability and triggered apoptosis in PANC-1 pancreatic cancer cell line dependent on PP2A/IKK alpha/I kappa B alpha/p65 NF-kappa B pathway. The activation of NF-kappa B pathway up-regulated downstream pro-apoptotic genes, TNF-alpha, TRAILR1 and TRAILR2, and triggered apoptosis through the extrinsic pathway, indicating that PP2A is a potential target for pancreatic cancer treatment. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

引用

页码：117 / 127

页数：11

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