Apatinib suppresses the migration, invasion and angiogenesis of hepatocellular carcinoma cells by blocking VEGF and PI3K/AKT signaling pathways

Mol Med Rep. 2021 Jun;23(6):429. doi: 10.3892/mmr.2021.12068. Epub 2021 Apr 13.

Abstract

Hepatocellular carcinoma (HCC) is a commonly diagnosed malignancy worldwide with poor prognosis and high metastasis and recurrence rates. Although apatinib has been demonstrated to have potential antitumor activity in multiple solid tumors, the underlying mechanism of apatinib in HCC treatment remains to be elucidated. In the present study, apatinib were used to treat HCC cells transfected with or without VEGFR2 overexpression vectors. The proliferation of HCC cells was detected by MTT assay. The migration and invasion of HCC cells were detected by wound healing assay and Transwell assay. The ability of angiogenesis of HCC cells were detected by tube formation assay. The related protein expression levels were detected by western blotting. The present study aims to investigate the effect and potential mechanism of apatinib on the migration, invasion and angiogenesis of HCC cells. It was found that apatinib treatment significantly inhibited the proliferation, migration and invasion of Hep3b cells and suppressed angiogenesis in HUVECs. In addition, apatinib inhibited the epithelial‑mesenchymal transition of Hep3b cells by increasing the expression of the epithelial hallmarks E‑cadherin and α‑catenin and decreased the expression of the mesenchymal hallmarks N‑cadherin and vimentin. These effects were associated with the downregulation of VEGF and VEGFR2 and suppression of the PI3K/AKT signaling pathway. Thus, apatinib inhibited cell migration, invasion and angiogenesis by blocking the VEGF and PI3K/AKT pathways, supporting an effective therapeutic strategy in the treatment of HCC.

Keywords: hepatocellular carcinoma; apatinib; VEGF; PI3K/AKT.

MeSH terms

  • Angiogenesis Inducing Agents / pharmacology*
  • Angiogenesis Inhibitors / pharmacology
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Pyridines / pharmacology*
  • Receptors, Vascular Endothelial Growth Factor / drug effects*
  • Receptors, Vascular Endothelial Growth Factor / metabolism
  • Signal Transduction
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism
  • Wound Healing / genetics

Substances

  • Angiogenesis Inducing Agents
  • Angiogenesis Inhibitors
  • Pyridines
  • apatinib
  • Receptors, Vascular Endothelial Growth Factor
  • Vascular Endothelial Growth Factor Receptor-2
  • Proto-Oncogene Proteins c-akt

Grants and funding

This work was supported by the Qingdao Health Science and Technology Project (grant no. 2016-WJZD076).