基础医学与临床 ›› 2008, Vol. 28 ›› Issue (12): 1260-1265.

• 研究论文 • 上一篇    下一篇

JAK2抑制剂AG490对食管癌细胞增殖、凋亡及COX-2表达的影响

刘俊茹 左连富 杨建柱 王莹 刘淑霞 王冬   

  1. 河北医科大学第三医院 河北医科大学病理教研室
  • 收稿日期:2008-03-03 修回日期:2008-04-16 出版日期:2008-12-25 发布日期:2008-12-25
  • 通讯作者: 刘俊茹

JAK2/STAT3 signaling pathway mediating proliferation, apoptosis and COX-2 expression of esophageal carcinoma Eca-109 cell line

Jun-ru LIU, Lian-fu ZUO, Jian-zhu YANG, Ying WANG, Shu-xia LIU, Dong WANG   

  1. the Third Hospital, Hebei Medical University Hebei Medical University
  • Received:2008-03-03 Revised:2008-04-16 Online:2008-12-25 Published:2008-12-25
  • Contact: Jun-ru LIU,

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;Western blot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-2 mRNA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-2 mRNA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。

关键词: Eca-109细胞, JAK2/STAT3, 增殖, 凋亡, COX-2

Abstract: Objective To investigate the relationship between STAT3 signal transduction pathway and proliferation as well as apoptosis and COX-2 expression of human esophageal carcinoma Eca-109 cell lines. Methods Eca-109 cells were treated with selective JAK2 inhibitor, AG490. MTT 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 protein expressions of JAK2、p-JAK2、p-Stat3 and COX-2 were 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 could inhibit the expressions of JAK2/STAT3 signal transduction pathway protein and down-regulate 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). Conclusions 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 proliferative inhibition in Eca-109 cells. This may be a new target of selective JAK2 inhibitor effect on Eca-109 cells.

Key words: Eca-109 cells, JAK2/STAT3, prolifertion, apoptosis, COX-2

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