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

阿帕替尼通过调控NF-κB信号通路下调MMP相关蛋白抑制肝癌细胞侵袭转移

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作者:Xiaoxiao He, Zaozao Huang, Ping Liu, Qiuting Li, Mengmeng Wang, Mengjun Qiu, Zhifan Xiong, Shengli Yang

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.

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.

Objective

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

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.

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