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

Biomed Res Int. 2020 Jun 19:2020:3126182. doi: 10.1155/2020/3126182. eCollection 2020.

Abstract

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.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Humans
  • I-kappa B Proteins / antagonists & inhibitors*
  • I-kappa B Proteins / metabolism
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Matrix Metalloproteinases / metabolism*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Phosphorylation
  • Protein Kinase Inhibitors / pharmacology
  • Pyridines / pharmacology*
  • Signal Transduction / drug effects
  • Transcription Factor RelA / antagonists & inhibitors*
  • Transcription Factor RelA / metabolism

Substances

  • I kappa B beta protein
  • I-kappa B Proteins
  • Protein Kinase Inhibitors
  • Pyridines
  • Transcription Factor RelA
  • apatinib
  • Matrix Metalloproteinases