Apatinib Inhibits the Invasion and Metastasis of Liver Cancer Cells by Downregulating MMP-Related Proteins via Regulation of the NF-κB Signaling Pathway

الملخص EN

Objective.

We aimed to investigate whether apatinib has an inhibitory effect on the invasion and metastasis of liver cancer in vitro.

Methods.

The anti-invasion and antimetastasis effects of apatinib in HepG2, Hep3B,Huh7 and SMMC-7721 liver cancer cell lines were tested by the wound-healing and transwell invasion assays.

Real-time PCR and Western blot were used to detect the influence of apatinib on the gene expression of MMPs, TIMPs, and constituents of the NF-κB signaling pathway in Hep3B and HepG2 liver cell lines.

Results.

Apatinib has a significant inhibitory effect on the metastasis and invasion of liver cancer cells.

The expression levels of MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-10, MMP-11, and MMP-16 were downregulated, while the expression levels of TIMP-3 and TIMP-4 were upregulated by apatinib treatment at both the mRNA and protein levels.

The phosphorylation of IκBα and NF-κB p65 was significantly reduced compared with that in the control group.

Conclusions.

Apatinib inhibits the invasion and metastasis of human liver cancer cells by downregulating the expression of MMP-related genes.

This may be achieved by inhibiting the activation of the NF-κB signaling pathway.