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AG490对人胰腺癌细胞体外侵袭和转移的抑制作用

[Inhibitory effect of AG490 on invasion and metastasis of human pancreatic cancer cells in vitro].

作者信息

Huang Chen, Qiu Zheng-Jun, Cao Jun, Huang Ke-Jian, Zhang Fang, Jiang Tao, Zhu Lin, Liu Jun

机构信息

Department of General Surgery, Affiliated First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, China.

出版信息

Zhonghua Zhong Liu Za Zhi. 2006 Dec;28(12):890-3.

Abstract

OBJECTIVE

To investigate the effect and mechanism of blockade of STAT3 signaling pathway by JAK specific inhibitor-AG490 on invasion and metastasis of human highly metastatic pancreatic cancer line SW1990 in vitro.

METHODS

AG490 was added into the culture media for SW1990 cells. The invasion ability of SW1990 cells was determined by cell invasion assay kit. Western blot was performed to detect the protein expression of the STAT3, phosphorylated STAT3 (p-STAT3), MMP-2 and VEGF. RT-PCR was performed to detect the mRNA expression of the MMP-2 and VEGF.

RESULTS

20 micromol/L AG490 significantly inhibited the invasion ability of SW1990 cells and the inhibitory rate of invasion ability was (77.67 +/- 7.79) %. The use of AG490 not only markedly reduced the protein expression of p-STAT3, MMP-2 and VEGF, but also greatly reduced the mRNA expression of MMP-2 and VEGF.

CONCLUSION

Blocking STAT3 activation with AG490 can inhibit the invasion and metastasis ability of pancreatic cancer cells in vitro through down-regulation of MMP-2 and VEGF expression. Blocking STAT3 signaling pathway may provide a novel strategy in prevention of invasion and metastasis of pancreatic cancer.

摘要

目的

探讨JAK特异性抑制剂AG490阻断STAT3信号通路对人高转移胰腺癌细胞系SW1990体外侵袭和转移能力的影响及其机制。

方法

将AG490加入SW1990细胞的培养基中。采用细胞侵袭实验试剂盒检测SW1990细胞的侵袭能力。进行蛋白质印迹法检测STAT3、磷酸化STAT3(p-STAT3)、基质金属蛋白酶-2(MMP-2)和血管内皮生长因子(VEGF)的蛋白表达。进行逆转录-聚合酶链反应(RT-PCR)检测MMP-2和VEGF的mRNA表达。

结果

20 μmol/L AG490显著抑制SW1990细胞的侵袭能力,侵袭能力抑制率为(77.67±7.79)%。使用AG490不仅显著降低了p-STAT3、MMP-2和VEGF的蛋白表达,还大幅降低了MMP-2和VEGF的mRNA表达。

结论

用AG490阻断STAT3激活可通过下调MMP-2和VEGF表达来抑制胰腺癌细胞的体外侵袭和转移能力。阻断STAT3信号通路可能为预防胰腺癌的侵袭和转移提供一种新策略。

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