抑制信号转导与转录激活因子-3基因表达对人胰腺癌细胞转移能力的影响  

Effect of RNAi-mediated STAT3 gene inhibition on metastasis of human pancreatic cancer cells

作　　者：高臻[1] 黄陈[1] 裘正军[1] 江弢[1] 朱麟[1] 曹俊[1] 张放[1] 黄克俭[1] 

机构地区：[1]上海交通大学附属第一人民医院普外科,200080

出　　处：《中华外科杂志》2008年第13期1010-1013,共4页Chinese Journal of Surgery

基　　金：上海市教育委员会科研资助项目（06BZ067）

摘　　要：目的探讨RNA干扰（RNAi）技术抑制信号转导与转录激活因子-3（STAT3）表达对人胰腺癌细胞株SW1990体内转移能力的影响及其机制。方法构建STAT3短发卡RNA（shRNA）表达载体，稳定转染SW1990细胞。应用RT-PCR方法观察STAT3mRNA表达的改变，EMSA方法检测STAT3-DNA结合活性的改变。应用裸鼠急性血路转移实验检测细胞体内转移能力的变化，并通过RT-PCR方法检测基质金属蛋白酶-2（MMP-2）和血管内皮生长因子（VEGF）mRNA表达的改变。结果STAT3shRNA表达载体稳定转染SW1990细胞可显著抑制STAT3mRNA表达和STAT3-DNA结合活性（P〈0．05）；裸鼠急性血路转移实验显示，RNAi技术抑制STAT3后，SW1990细胞体内转移能力明显下降（P〈0．05）；RT—PCR结果显示，RNAi技术抑制STAT3后，SW1990细胞中MMP-2和VEGF的mRNA表达明显减低（P〈0．05）。结论RNAi技术能有效抑制STAT3基因表达，并可通过下调MMP-2和VEGF表达抑制胰腺癌细胞体内转移能力。Objective To investigate the effect of RNAi-mediated STAT3 gene inhibition on metastasis of human pancreatic cancer cells and its underlying mechanism. Methods STAT3 shRNA expression vector was constructed and transfected into SW1990 cells. STAT3 mRNA and STAT3 DNA- binding activity were examined using reverse transcription polymerase chain reaction （RT-PCR） and electrophoretic mobility shift assay（EMSA） ,respectively. The metastasis ability of SW1990 cells in vivo was determined in acute hematal metastasis model using nude mice. RT-PCR was performed to detect the mRNA expression of the MMP-2 and VEGF. Results The mRNA expression of STAT3 and STAT3 DNA-binding activity were inhibited significantly by stable transfection of STAT3 shRNA expressing vectors. RNAi inhibition of STAT3 significantly suppressed the metastasis ability of SW1990 cells in vivo, and alsomarkedly reduced the mRNA expression of MMP-2 and VEGF in SW1990 cells. Conclusions Inhibition of STAT3 by RNAi significantly inhibits the metastasis ability of pancreatic cancer cells through down-regulation of MMP- 2 and VEGF, and may provide a novel strategy for preventing the metastasis of pancreatic cancer.

关 键 词：胰腺肿瘤 肿瘤 实验性 RNA干扰 转移 

分 类 号：R686[医药卫生—骨科学]