蛋白磷酸酶2A抑制剂通过核因子-κB通路诱导胰腺癌细胞株PANC-1凋亡  

PP2A inhibitors trigger apoptosis of pancreatic cancer PANC-1 cells through nuclear factor-κB-de- pendent pathway

作　　者：李伟[1,2] 陈政[1] 龚斐然[3] 苗毅[1] 陶敏[2] 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肿瘤科 [3]苏州大学附属第一医院血液科

出　　处：《中华实验外科杂志》2011年第10期1720-1722,共3页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目（81072031）;江苏省“六大人才高峰”项目[2007200（E107）]

摘　　要：目的探讨蛋白磷酸酶2A（PP2A）抑制剂斑蝥素和冈田酸通过激活核因子-κB（NF-κB）通路诱导胰腺癌细胞株PANC-1凋亡的作用机制。方法PP2A抑制剂处理胰腺癌细胞后，噻唑蓝（MTT）检测细胞活力，流式细胞术检测凋亡水平，Westernblot检测NF-κB通路的激活水平。结果PP2A抑制剂显著抑制胰腺癌细胞活力，呈剂量和时间依赖性，并可诱导细胞凋亡；PP2A抑制剂激活NF-κB通路的上游激酶IKKα，导致IKBα磷酸化并降解，并释放p65入核，从而激活NF-κB通路；阻断NF-κB通路，可削弱PP2A抑制剂的细胞毒性作用。结论PP2A抑制剂通过NF-κB通路依赖性机制诱导胰腺癌细胞凋亡，有望用于胰腺癌治疗。Objective To investigate the action mechanism of protein phosphatase 2A （PP2A） inhibitors inducing apoptosis of pancreatic cancer cell line PANC-1. Methods Cell viability was deter- mined by methyl thiazol tetrazolium （MTT） assay. Activation of nuclear factor-κB （NF-κB） pathway was tested by Western blotting. Apoptosis was tested by flow cytometry. Results Treatment with PP2A inhibitots repressed the cell viability of PANC-1 cells in a dose- and time-dependent manner. PP2A inhibitors also triggered apoptosis in pancreatic cancer cells. Treatment with PP2A inhibitors induced activation of NF-KB pathway through phosphorylation of IKKoL, phosphorylation and degradation of IKBα, and nuclear translocation of p65. The cytotoxicity of PP2A inhibitors could be attenuated by the inhibitor of NF-KB pathway. Conclusion PP2A inhibitors triggered apoptosis of pancreatic cancer cells through NF-κB-de- pendent pathway, making PP2A an attractive target for pancreatic cancer therapy.

关 键 词：PP2A抑制剂 胰腺癌 核因子-ΚB 

分 类 号：R735.9[医药卫生—肿瘤]