JAK2抑制剂对食管癌细胞增殖、凋亡及COX-2表达的影响  

Effect of JAK2 inhibitor on proliferation,apoptosis and COX-2 expression of esophageal carcinoma Eca-109 cell line

作　　者：刘俊茹[1] 左连富[2] 杨建柱[1] 王莹[1] 刘淑霞[3] 王冬[1] 

机构地区：[1]河北医科大学第三医院病理科,河北石家庄050051 [2]河北医科大学第四医院肿瘤研究所,河北石家庄050011 [3]河北医科大学病理教研室,河北石家庄050017

出　　处：《基础医学与临床》2008年第12期1260-1265,共6页Basic and Clinical Medicine

基　　金：河北省科技厅科技攻关项目(05276172)

摘　　要：目的研究食管癌细胞Eca-109增殖、凋亡及COX-2表达与信号转导子和激活子3(STAT3)信号传导通路的关系,明确以JAK2/STAT3为靶向的信号转导在Eca-109细胞中的分子调控机制。方法将JAK2抑制剂AG490作用于Eca-109细胞,用MTT法检测细胞增殖;流式细胞仪、DNA琼脂糖电泳法及透射电子显微镜检测细胞凋亡;Westernblot法检测细胞中JAK2、p-JAK2、p-Stat3及COX-2的蛋白表达变化;RT-PCR检测COX-2mRNA的变化。结果AG490呈时间、剂量依赖性的抑制Eca-109细胞增殖并诱导凋亡,抑制JAK2/STAT3通路蛋白的表达,呈浓度依赖性地下调p-JAK2及p-Stat3蛋白的表达(P<0.05),并下调COX-2mRNA及蛋白的表达(P<0.05)。结论JAK2/STAT3信号传导通路调控AG490对Eca-109细胞作用的细胞内信号传导机制,最终通过下调COX-2表达影响Eca-109细胞的增殖并诱导凋亡。Objective To investigate the relationship of STAT3 signal transduction pathway with proliferation, apoptosis and COX-2 expression of human esophageal carcinoma Eca-109 cell lines. Methods Eca-109 cells were treated with selective JAK2 inhibitor, AG490. MTr assay was used to detect the proliferation of Eca-109 cells, apoptosis was detected by flow cytometry, agarose gel electrophoresis of DNA and transmission electron micrograph （TEM）. The expression of JAK2, p-JAK2, p-Stat3 and COX-2 was examined by Western blot. RT-PCR was performed to detect the levels of COX-2 mRNA expression. Results AG490 significantly inhibited the growth of human Eca-109 cells in a dose and time-dependent manner and induced apoptosis. AG490 inhibited the expres- sions of JAK2/STAT3 signal transduction pathway protein and down-regulated the expressions of p-JAK2 and p-Stat3 （P 〈 0. 05）, meanwhile, AG490 also reduced the expression of COX-2 mRNA and protein （P 〈 0. 05）. Conclusion AG490 may inhibit the proliferation and induce apoptosis of Eca-109 cells through decreasing expression of JAK2, STAT3 and COX-2. JAK2/STAT3 signaling pathway mediate AG490 induce apoptosis and prolifera- tive inhibition in Eca-109 cells.

关 键 词：ECA-109细胞 JAK2/STAT3 增殖 凋亡 COX-2 

分 类 号：R735.1[医药卫生—肿瘤]