摘要
目的探讨胰腺癌中信号传导和转录激活因子3(signal transduction and activators oftranscription-3,STAT3)与基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)表达的相关性。方法免疫组织化学方法检测34例胰腺癌和10例正常胰腺组织中 STAT3、磷酸化 STAT3(p-STAT3)和 MMP-2的表达,分析 STAT3、p-STAT3和 MMP-2表达的关系。JAK 激酶抑制剂 AG490阻断胰腺癌细胞株 SW1990的 STAT3信号通路,电泳迁移率实验(electrophoretic mobility shift assay,EMSA)和Western blot 分别检测 SW1990细胞中 STAT3-DNA 结合活性和 p-STAT3蛋白表达的变化;Western blot和 RT-PCR 分别检测 SW1990细胞中 MMP-2蛋白和 mRNA 的表达的变化。结果免疫组织化学发现 STAT3、p-STAT3和 MMP-2在胰腺癌组织中存在高表达,且 p-STAT3与 MMP-2的表达呈正相关(r=0.583,P=0.000)。AG490阻断 STAT3通路可抑制 SW1990细胞中 STAT3-DNA 结合活性和p-STAT3蛋白表达;同时 MMP-2蛋白和 mRNA 表达水平也明显降低。结论胰腺癌中 STAT3信号通路与 MMP-2表达密切相关;阻断 STAT3信号转导通路可能为预防和治疗胰腺癌的侵袭转移提供一种新的策略。
Objective To investigate the correlation between the expression of STAT3 and MMP-2 in human pancreatic cancer, and to probe the mechanism by which STAT3 signal pathway regulates the expression of MMP-2 in pancreatic cancer cells. Methods Immunohistochemistry was used to detect the expression of STAT3 ,phosphorylated STAT3 （ p-STAT3 ） and MMP-2 in pancreatic cancer tissues of 34 cases and normal pancreatic tissues of 10 cases. Correlation between the expression of STAT3,p-STAT3 and MMP- 2 were statistically analyzed. Human pancreatic cancer cell lines SW1990 was cultured. AG490, an inhibitor of the upstream Janus kinase （JAK） of STAT3 was added into the culture medium. Electrephoretic mobility shift assay （EMSA） was used to detect STAT3 DNA-binding activity in SW1990 cells. Western blot was used to detect the expression of STAT3, p-STAT3 in SW1990 cells. In addition, the protein and mRNA expression of MMP-2 in SW1990 cells were determined by Western blot and RT-PCR, respectively. Results Immunohistochemistry revealed that the expression rate of STAT3, p-STAT3 were both higher in pancreatic cancer tissues than in normal pancreas tissues （ P 〈 0. 05 ）. MMP-2 expression was higher in pancreatic cancer tissues than in normal pancreas tissues （ P 〈 0.05 ）. The expression of p-STAT3 was positively correlated with that of MMP-2 as tested with Spearman rank correlation （ r = 0. 583, P = 0. 000）. In addition, AG490 significantly inhibited STAT3 DNA-binding activity and the expression of p-STAT3 protein. Moreover, the use of AG490 not only markedly reduced the protein expression of MMP-2 but also greatly reduced the mRNA expression of MMP-2. Conclusion STAT3 signal pathway correlates with the expression of MMP-2 in pancreatic cancer. Blocking STAT3 signaling pathway may prevent the invasion and metastasis of pancreatic cancer.
出处
《中华普通外科杂志》
CSCD
北大核心
2007年第12期932-935,共4页
Chinese Journal of General Surgery
关键词
胰腺癌
信号传导
转录
基质金属蛋白酶-2
转移
Pancreatic neoplasms
Signal transduction
Transcription
Matrix metalloproteinase-2
Metastasis
