JAK2/STAT3通路在肝癌细胞侵袭及血管生成拟态中的作用

Role JAK2/STAT3 signaling pathway in invasion and vascular mimicry of liver cancer cells

目的探讨JAK2/STAT3通路在肝癌细胞QGY-7701侵袭及血管生成拟态中的作用。方法 JAK2抑制剂AG490(5、10μmol/L)处理肝癌细胞48 h,Transwell小室、体外成管实验分别检测各组细胞的体外侵袭能力和成管能力,RT-PCR检测Twist1及MMP-2 mRNA表达差异,Western blot检测STAT3、p-STAT3、Twist1和MMP-2蛋白表达差异。结果与对照组相比,Transwell小室穿膜细胞数减少,形成管道结构数目减少,Twist1及MMP-2 mRNA表达减少,Twist1、MMP-2和p-STAT3蛋白表达减少,差异均有统计学意义(P<0.05),STAT3蛋白表达无差异(P>0.05)。结论 AG490能有效抑制肝癌细胞侵袭及成管的能力,JAK2/STAT3通路在肝癌细胞侵袭及血管生成拟态中起促进作用。

Objective To determine the role of JAK2/STAT3 signaling pathway in invasion and vas- cular mimicry of liver cancer cell line QGY-7701. Methods After QGY-7701 cells were treated with 5 and 10 lxmol/L AG490 （ the inhibitor of JAK2） for 48 h, the invasion and tube formation of tumor cells were tested with Transwell chamber test and vascular mimicry experiment. RT-PCR was used to measure the expression of Twistl and MMP-2, and Western blot assay was employed to determine the expression of p-STAT3, STAT3, Twistl and MMP-2. Results Compared to control group, there were less tumor ceils permeating membrane and less formed tubes after AG490 treatment. RT-PCR showed that the expression of Twistl and MMP-2 at mR- NA level were decreased. Western blotting indicated that the expression of p-STAT3, Twistl, MMP-2 at protein levels were also decreased （P 〈 0. 05 ）, while that of STAT3 protein had no difference among each group （P 〉 0. 05）. Conclusion AG490 significantly inhibits invasion and vascular mimicry of liver cancer ceils in vitro, and JAK2/STAT3 signaling pathway promotes above processes.