激活和抑制Stat3信号途径对胰腺癌细胞侵袭能力的影响  

Effects of activation and inhibition of Stat 3 signaling pathway on invasion of human pancreatic cancer cells

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

机构地区：[1]上海交通大学附属第一人民医院普外科,上海200080

出　　处：《肿瘤》2009年第7期645-649,共5页Tumor

基　　金：上海市教育委员会科研资助项目(编号:06BE067)

摘　　要：目的:通过激活和阻断人胰腺癌细胞中的Stat3信号转导通路,观察细胞株侵袭能力的变化并探讨其作用机制。方法:采用IL-6处理人胰腺癌细胞Capan-2,AG490处理人胰腺癌细胞SW1990后,MTT法检测细胞的增殖状态,免疫细胞化学法和Western印迹法检测p-Stat3的表达,实时荧光定量PCR(real-time fluorogentic quantitative PCR,RFQ-PCR)和Western印迹法检测血管内皮生长因子(vascular endothelial growth factor,VEGF)、基质金属蛋白酶-2(matrix metalloproteinase 2,MMP-2)mRNA及其蛋白的表达,体外侵袭实验检测细胞的侵袭能力。结果:IL-6可促进Capan-2细胞的增殖能力提高(P<0.05),p-Stat3的表达增强,VEGF和MMP-2mRNA和蛋白表达明显升高(P<0.05),细胞侵袭能力增强。AG490可抑制SW1990细胞株的增殖(P<0.05),p-Stat3的表达下降,VEGF和MMP-2 mRNA和蛋白表达明显下降(P<0.05),侵袭能力减弱。结论:Stat3信号转导通路在胰腺癌侵袭过程中起着重要作用,以Stat3信号转导通路为靶点的基因治疗可能为胰腺癌治疗提供新的方向。Objective： In order to investigate the effects of activating and blocking Stat3 signaling pathway on invasion ability of human pancreatic cancer cells and explore its action mechanism. Methods ： Human pancreatic cancer Capan-2 cells were treated with IL-6. SW1990 human pancreatic cancer ceils were treated with AG490. Cell proliferation was measured by MTT assay. Western blotting and immunocytochemistry were performed to detect expression of phosphorylated Stat3 （p-Stat3） protein. Real-time fluorogentic quanti-tative PCR （RFQ-PCR） and Western blotting were used to detect the mRNA and protein expression of VEGF and MMP-2 mRNA, respectively. The invasion abilities of SW1990 and Capan-2 cells were determined by cell invasion assay in vitro. Results：IL-6 stimulated the proliferation of Capan-2 cells （P 〈 0.05）, elevated the expression of p-Stat3, increased the mRNA and protein expressions of vascular endothelial growth factor （VEGF） and matrix metalloproteinase 2 （ MMP-2 ） （ P 〈 0.05 ）, and enhanced the invasion ability of Capan-2 cells. AG490 inhibited the proliferation of SW1990 cells （ P 〈 0.05 ） , down-regulated the expression of p-Stat3, markedly decreased the mRNA and protein expression of VEGF and MMP-2 （P 〈 0.05 ） , and weakened the invasion ability of SW1990 cells. Conclusion ： Stat 3 signaling pathway plays an important role in the invasion and metastasis of pancreatic cancer. Stat 3 signaling trans-duction pathway may provide a novel therapeutic target for the treatment of pancreatic cancer.

关 键 词：胰腺肿瘤 STAT3转录因子 肿瘤浸润 Capan-2细胞 SW1990细胞 

分 类 号：R735.9[医药卫生—肿瘤]