Apatinib exerts anti-tumour effects on ovarian cancer cells

Gynecol Oncol. 2019 Apr;153(1):165-174. doi: 10.1016/j.ygyno.2019.01.010. Epub 2019 Jan 14.

Abstract

Objective: Apatinib, a small molecule inhibitor of VEGFR-2 tyrosine kinase, shows strong anti-tumour activity against various tumours. The function of apatinib in ovarian cancer, however, remains unclear. This study was conducted to investigate the effects and potential mechanisms by which apatinib modulates the biological function of ovarian cancer cells in vitro and in vivo.

Methods: The effects of apatinib on ovarian cancer cells were determined by assessing cell viability, migration and invasion. The cell cycle distribution and apoptosis of ovarian cancer cells were analysed using flow cytometry. Western blotting was performed to determine the levels of signalling pathway markers. A mouse xenograft model was used to evaluate the efficacy of apatinib in preventing tumour growth.

Results: Apatinib did not appreciably affect ovarian cancer cell proliferation and vitality, but did inhibit ovarian cancer cell migration. Apatinib suppressed the epithelial-mesenchymal transition in ovarian cancer cells by inhibiting the JAK/STAT3, PI3K/AKT and Notch signalling pathways. Apatinib effectively inhibited tumour growth in vivo.

Conclusion: Based on our findings, apatinib is a highly potent, orally active anti-angiogenic and anti-ovarian cancer agent.

Keywords: Apatinib; Cell migration; Epithelial-mesenchymal transition; Ovarian cancer; Signalling pathway.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Carcinoma, Ovarian Epithelial / drug therapy*
  • Carcinoma, Ovarian Epithelial / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Pyridines / pharmacology*
  • Random Allocation
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Pyridines
  • apatinib