AG490抑制人胰腺癌细胞侵袭转移的体外研究

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

目的探讨Janus激酶抑制剂AG490对高转移潜能人胰腺癌细胞系SW1990体外侵袭转移能力的影响及其机制。方法用AG490处州SW1990细胞,细胞侵袭测定试剂盒检测细胞侵袭能力,Western blot检测信号传导与转录激活因子3(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)蛋白的表达,RT-PCR检测MMP-2 mRNA和VEGF mRNA的表达。结果20μmol／L AG490可显著抑制SW1990细胞侵袭能力,侵袭抑制率为(77．67±7．79)％。Western blot显示,p-STAT3、MMP-2和VEGF的蛋白表达在SW1990细胞中明显减低。RT- PCR显示,MMP-2 mRNA和VEGF mRNA在SW1990细胞中亦明显减低。结论AG490通过阻断STAT3活化,下调MMP-2和VEGF表达,抑制胰腺癌细胞体外侵袭转移能力。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 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 ceils. 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 20μmol/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.