阿司匹林促进干扰素-α诱导肝癌凋亡的作用机制  

Aspirin enhances IFN-a-induced apoptosis of hepatocellular carcinoma

作　　者：李涛[1] 乔筱玲 王敏[3] 董兆如[4] 李登科[1] 陈泽婷[1] 陈阳[1] 陈志强[1] 智绪亭[1] 

机构地区：[1]山东大学齐鲁医院普外科,济南250012 [2]不详 [3]淄博市中心医院肿瘤科 [4]复旦大学附属中山医院肝癌研究所,上海

出　　处：《中华肝胆外科杂志》2014年第9期670-674,共5页Chinese Journal of Hepatobiliary Surgery

基　　金：国家自然科学基金（30972889）

摘　　要：目的 探讨阿司匹林协同干扰素-α（干扰素-α）诱导肝细胞癌（HCC）凋亡的作用机制.方法 体外培养人肝细胞癌Bel-7402细胞,分别以阿司匹林和IFN-α单独或联合作用于Bel-7402肝癌细胞.蛋白印迹检测细胞JAK/STAT通路相关蛋白JAK1 、JAK2 、TYK2、STAT1和STAT3的表达及磷酸化水平,并采用JAK2抑制剂AG490抑制JAK2的活性.RT-PCR检测阿司匹林和干扰素-α作用前后细胞IFN刺激性应答基因（IFN-stimulated gene,ISG）XAF1及G1P3等的转录水平.结果 IFN-α显著诱导STAT1和STAT3的磷酸化（P＜0.05）,阿司匹林可显著促进干扰素-α诱导的STAT1的磷酸化（P＜0.05）,但对IFN-α诱导的STAT3的磷酸化无显著影响.阿司匹林可显著促进IFN-α诱导JAK1和JAK2的磷酸化（P＜0.05）,但JAK2抑制剂AG490对阿司匹林协同IFN-α诱导的STAT1的磷酸化无抑制作用.此外,阿司匹林还可显著促进IFN-α诱导的XAF1 mRNA的转录而抑制G1P3mRNA的转录（P＜0.05）.结论 阿司匹林可通过激活JAK1/STAT1通路,上调促凋亡基因XAF1mRNA的转录及下调抗凋亡基因G1P3 mRNA的转录而发挥促进IFN-α诱导肝癌凋亡的作用.Objective To investigate the mechanism of aspirin in enhancing IFN-α induced apoptosis of hepatocellular carcinoma （HCC）.Methods Bel-7402 HCC cells were cultured and treated with IFN-a and/or aspirin.The expressions and phosphorylation of JAK1,JAK2,TYK2,STAT1 and STAT3 were evaluated by Western blot,and AG490 was used to inhibit the activity of JAK2.The transcriptions of IFN-stimulated gene （ISG） mRNAs,such as XAF1 and G1P3,were evaluated by RT-PCR.Results Although IFN-a alone resulted in significant phosphorylation of both STAT1 and STAT3,aspirin only prompted the IFN-a induced phosphorylation of STAT1.Aspirin also significantly prompted the IFN-a induced phosphorylation of JAK1 and JAK2.After blocking the activity of JAK2 by AG490,the phosphorylation of STAT1 induced by combined use of IFN-a and aspirin was not influenced significantly.Furthermore,aspirin significantly upregulated the transcription of X-linked inhibitor of apoptosis-associated factor-1 （XAF1） and downregulated the transcription of G1P3 induced by IFN-a.Conclusion Aspirin upregulated the transcription of XAF1 and downregulated the transcription of G1P via JAK1/STAT1 pathway,thereby enhances IFN-a-induced apoptosis of HCC.

关 键 词：肝细胞癌 阿司匹林 干扰素-Α 凋亡 

分 类 号：R735.7[医药卫生—肿瘤]