乙型肝炎病毒对HepG2细胞侵袭的影响

Effect of HBV on the Invasion of HepG2 Cell

目的研究HBV全长对HepG2细胞侵袭相关基因表达及活性的影响，探讨HBV在整体水平对HepG2细胞侵袭的影响。方法采用定量PCR分析HBV对HepG2细胞MMP2、9和TIMP1-4基因转录的影响；通过明胶酶谱及反相明胶酶谱检测MMP2、MMP9及TIMPs的活性；应用体外侵袭小室法检测细胞的侵袭能力。结果HBV的复制可以促进HepG2细胞MMP2、MMP9、TIMP1和TIMP3基因的转录，抑制TIMP4基因转录，增强HepG2细胞MMP2、MMP9的活性并增强细胞中TIMP1、TIMP3功能，HBV稳定复制的细胞具有更强的体外侵袭能力。结论HBV可影响HepG2细胞MMPs和TIMPs的基因转录、表达及功能，促进HepG2细胞的体外侵袭，这可能与HBV相关的HCC侵袭转移密切相关。

Objective To explore the effect of HBV on expression and activity of invasion-relative genes and invasion ability of HepG2 cells. Methods Human hepatoblastoma HepG2 cell line harboring 1.2 unit-length of HBV genome or containing only empty vector as control was used. The expression and activity of MMP2, MMP9, TIMP1, 2, 3, and 4 were detected by real-time PCR, gelatin zymography or reverse zymography. In vitro invasion ability was measured by Matrigel transwell invasion assay. Results The replication of full-length of HBV genome up-regulated expression of MMP2, MMP9, TIMP1, TIMP4, down-regulated expression of TIMPd, increased activity of MMP2, MMP9, TIMP1, TIMP3, and then promoted invasion ability of HepG2 cells, as compared with the empty vector control. Conclusion HBV genome influences invasion ability of HepG2 cells by deregulation of MMPs and TIMPs replication, which may provide new insights into the role of HBV in metastasis of hepatocellular carcinoma.