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蛋白磷酸酶2A抑制剂通过核因子-κB通路激活胰腺癌细胞外源性凋亡通路的机制 被引量:2

Protein phosphatase 2A inhibitors activate extrinsic apoptosis in pancreatic cancer cells through nu-clear factor-κB dependent pathway
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摘要 目的探讨蛋白磷酸酶2A(PP2A)抑制剂通过激活核因子-κB(NF-κB)通路诱导胰腺癌细胞株人胰腺癌细胞(PANC,1)凋亡的机制。方法荧光素酶报告基因检测NF.KB通路的激活水平,试剂盒检测半胱氨酰天冬氨酸特异性蛋白酶(Caspase)-8、9活性,逆转录-聚合酶链反应(RT-PCR)检测NF-κB通路下游凋亡相关基因表达水平。结果PP2A抑制剂斑蝥素、冈田酸可激活NF-κB通路,分别使NF-κB转录活性上升(10.11±4.09)倍、(16.21±5.75)倍。NF-κB通路抑制剂Bay11-7082预处理,可分别使斑蝥素、冈田酸诱导的NF-κB转录活性上升幅度下降(61.19±6.08)%、(62.09±12.38)%;斑蝥素、冈田酸可激活外源性凋亡通路,分别使Caspase-8活性上升(0.55±0.12)倍、(0.85±0.21)倍。Bay11-7082预处理,可分别使斑蝥素、冈田酸诱导的Caspase-8活性上升幅度下降(20.99±7.13)%、(29.07±7.98)%;斑蝥素、冈田酸可激活内源性凋亡通路,分别使Caspase-9活性上升(1.35±0.20)倍、(1.18±0.19)倍,但Bay11-7082预处理,对斑蝥素、冈田酸诱导的Caspase-9活性上升幅度无明显影响;斑蝥素、冈田酸可上调促凋亡基因的表达;Bay11-7082预处理可抑制斑蝥素、冈田酸诱导的促凋亡基因表达上调。结论PP2A抑制剂通过NF-κB通路依赖性机制激活胰腺癌细胞外源性凋亡通路,并上调促凋亡基因的表达。 Objective To investigate the apoptosis induction effect of protein phosphatase 2A (PP2A) inhibitors on human pancreatic cancer cell line (PANC-1). Methods Activity of nuclear factor-κB (NF-κB) pathway was tested by using luciferase reporter gene assay. Activities of Caspase 8 and 9 were determined by kits. The expression levels of genes downstream of the NF-κB pathway were tested by u- sing reverse transcription-polymerase chain reaction (RT-PCR). Results Treatment with PP2A inhibitors, eantharidin and Okadaic acid, up-regulated the transcriptional activity of NF-κB by the folds of 10. 11 ±4.09, and 16. 21 ± 5.75 respectively. Pretreatment with the NF-κB pathway inhibitor, Bay 11-7082, repressed the up-regulation of NF-κB transcriptional activity by (61.19 ± 6.08 )% and (62.09 ± 12. 38 )% respectively. Treatment with cantharidin or Okadaic acid activated extrinsic apoptosis pathway, and up-regu- lated the activity of Caspase 8 by the folds of 0. 55 ±0. 12, and 0. 85±0. 21 respectively. Pretreatment with Bay 11-7082 repressed the up-regulation of Caspase 8 activity by (20. 99 ±7. 13)% and (29. 07±7.98)% respectively. Treatment with cantharidin or Okadaic acid also activated intrinsic apoptosis pathway, and up-regulated the activity of Caspase 9 by the folds of 1.35±0. 20, and 1.18 ±0. 19 respectively. However, pretreat- ment with Bay 11-7082 presented no significant effect on the up-regulation of Caspase 9 activity. Treatment with cantharidin or Okadaic acid up-regnlated the expression of pro-apoptotic genes which could be repressed by the pretreatment with Bay 11-7082. Conclusion PP2A inhibitors triggered extrinsic apoptosis and up-regulated the expressions of pro-apoptotic genes in pancreatic cancer cells through NF-κB dependent pathway.
出处 《中华实验外科杂志》 CAS CSCD 北大核心 2012年第11期2215-2218,共4页 Chinese Journal of Experimental Surgery
基金 国家自然科学基金资助项目(81072031、81101867) 江苏省自然科学基金资助项目(BK2010585) 苏州市科教兴卫青年科技项目(SWKQl003、SWKQl011)
关键词 胰腺癌 蛋白磷酸酶2A 斑蝥素 核因子-ΚB Pancreatic cancer Protein phosphatase 2A Cantharidin Nuclear factor-KB
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