Janus激酶抑制剂AG490对人肝癌SMMC-7721细胞侵袭转移的影响

目的 研究Janus激酶抑制剂AG490对人肝癌SMMC-7721细胞侵袭转移能力的影响，探讨JAK2/STAT3信号通路在肝癌侵袭调控中的作用。方法实验分为对照组、实验组（5、10 μmol/L AG490处理的SMMC-7721细胞）。采用Transwell小室检测肝癌细胞的侵袭能力，RT-PCR检测MMP-2 m...

Effect of Janus kinase inhibitor AG490 on invasion and metastasis of human liver cancer SMMC-7721 cells

Objective To study the effect of Janus kinase(JAK) inhibitor AG490 on the invasion and metastasis of human liver cancer SMMC-7721 cells and the role of JAK-STAT3 signaling pathway in regulation of liver cancer invasion.Methods SMMC-7721 cells were divided into control group,5 μmol/L AG490 treatment group and 10 μmol/L AG490 treatment group.Invasion and metastasis of liver cancer SMMC-7721 cells were detected with transwell chamber.Expression of MMP-2 mRNA and VEGF mRNA in liver cancer SMMC-7721 cells was detected by RT-PCR.Expression and activation of STAT3,MMP-2 and VEGF proteins in liver cancer SMMC-7721 cells was detected by Western blotting.Results The number of membrane-permeating SMMC-7721 cells was 74.6±6.3,58.2±7.2,and 38.2±5.7 in control group,5 μmol/L AG490 treatment group,and 10 μmol/L AG490 treatment group,respectively,48 h after AG490 treatment.The ability of SMMC-7721 cells to invade the artificial basement membrane was significantly lower in two AG490 treatment groups than in control group(P<0.05).RT-PCR showed that the expression level of MMP-2 mRNA and VEGF mRNA was significantly lower in two AG490 treatment groups than in control group(P<0.05).Western blotting showed that the activation level of STAT3 protein and the expression level of MMP-2 and VEGF were lower in two AG490 treatment groups than in control group(P<0.05).Conclusion AG490 can down-regulate the expression of MMP-2 and VEGF by blocking the activation of STAT3,thus inhibiting the invasion of liver cancer SMMC-7721 cells in vitro.