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JAK2/STAT3信号转导通路参与调节IL-6介导的肺腺癌细胞株中MMP-10的表达
引用本文:银培基,狄冬梅,罗光华,郑璐,魏江,张俊,施媛萍,张继琛,张晓膺.JAK2/STAT3信号转导通路参与调节IL-6介导的肺腺癌细胞株中MMP-10的表达[J].中华临床医师杂志(电子版),2009,3(6):18-22.
作者姓名:银培基  狄冬梅  罗光华  郑璐  魏江  张俊  施媛萍  张继琛  张晓膺
作者单位:1. 苏州大学附属第三医院心胸外科,江苏常州,213003
2. 苏州大学附属第三医院综合实验室,江苏常州,213003
基金项目:常州市科技局指导性项目 
摘    要:目的研究Janus激酶2(JAK2)及信号转导和转录激活子3(STAT3)途径对IL-6介导的肺腺癌细胞(A549)中基质金属蛋白酶10(MMP-10)表达调节的作用,探讨MMP-10的调节机制。方法待生长状况良好的A549细胞融合生长至50%~70%时,分别用0,12.5,25,50ng/mlIL-6及AG490(JAK2特异性抑制剂)+25ng/mlIL-6处理A549细胞24h后,采用实时RT-PCR技术检测JAK2、STAT3和MMP-10mRNA的表达水平;应用Westernblot检测MMP-10蛋白的表达水平。结果25ng/mlIL-6组STAT3mRNA表达水平较0ng/ml组高43.87%(P〈0.05),AG490+25ng/mlIL-6组较25ng/mlIL-6组低36.73%(P〈0.01);AG490+25ng/mlIL-6组MMP-10mRNA表达水平较25ng/mlIL-6组高43.21%(P〈0.01);12.5,25,50ng/mlIL-6组的MMP-10蛋白水平显著高于0ng/ml组(P〈0.05),且峰值出现在25ng/ml组;与25ng/mlIL-6组相比,MMP-10蛋白水平在AG490+25ng/mlIL-6组明显降低(P〈0.05)。结论JAK2/STAT3信号转导途径可能参与调节IL-6介导的肺癌细胞株A549中MMP-10的表达。

关 键 词:肺肿瘤  Janus激酶2  STAT3转录因子  基质金属蛋白酶10  白细胞介素6

Up-regulation of MMP-10 expression is mediated by JAK2/STAT3 signaling pathway in human lung adenocarcinoma cell line
YIN Pei-ji,DI Dong-mei,LUO Guang-hua,ZHENG Lu,WEI Jiang,ZHANG Jun,SHI Yuan-ping,ZHANG Ji-chen,ZHANG Xiao-ying.Up-regulation of MMP-10 expression is mediated by JAK2/STAT3 signaling pathway in human lung adenocarcinoma cell line[J].Chinese Journal of Clinicians(Electronic Version),2009,3(6):18-22.
Authors:YIN Pei-ji  DI Dong-mei  LUO Guang-hua  ZHENG Lu  WEI Jiang  ZHANG Jun  SHI Yuan-ping  ZHANG Ji-chen  ZHANG Xiao-ying
Institution:. (Department of Thoracic and Cardiovascular Surgery, The Third Affiliated Hospital of Suzhou University, Changzhou 213003, China)
Abstract:Objective To investigate the role of JAK2/STAT3 in the expression of MMP-10 in human lung adenocarcioma cell line and explore the molecular regulatory mechanism of MMP-10 expression. Methods A549 cells were seeded in six-well cell culture clusters, and were grown to 50% - 70% confluence. 0,12. 5,25,50 ng/ml IL-6 and AG490 + 25 ng/ml IL-6 were given to A549 cells, respectively. The expression of JAK2, STAT3 and MMP-10 mRNA were detected with real-time RT-PCR assay. MMP-10 protein was determined by Western blot. Results In A549 cells,STAT3 mRNA levels at 25 ng/rnl IL-6 was higher than at 0 ng/ml IL-6 ( P 〈 0. 05 ). 50 ixmol/L AG490, a specific JAK2 inhibitor, together with 25 ng/ml IL-6 decreased STAT3 mRNA expression by 36. 73%, compared with 25 ng/ml IL-6 ( P 〈 0. 01 ). On the contrary, MMP-10 mRNA levels in 3.549 cells treated with 50/.Lmol/L AG490 + 25 ng/ml IL-6 were significantly higher than with 25 ng/ml IL-6 (P 〈 0. 01 ). MMP-10 protein levels at 12. 5,25,50 ng/ml IL-6 were significantly increased compared with 0 ng/ml IL-6 (P 〈 0. 05 ). 50 μmol/L AG490, together with 25 ng/ml IL-6 reduced MMP-10 protein expression compared with 25 ng/ml IL-6 (P 〈 0. 05). Conclusions It is suggested that the JAK2/ STAT3 pathway might be involved in the expression of MMP-10 in A549 cells.
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