Matrine derivative YF-18 inhibits lung cancer cell proliferation and migration through down-regulating Skp2

Oncotarget. 2017 Feb 14;8(7):11729-11738. doi: 10.18632/oncotarget.14329.

Abstract

Lung cancer is the leading cause of cancer related death which needs novel drugs to improve patient outcomes. In this study, we examined the ability of YF-18, a novel matrine derivative to inhibit the growth and migration of lung cancer cells. By cell cycle analysis, wound healing and transwell assays, we found that YF-18 induced G2/M cell cycle arrest and inhibited migration of lung cancer cells in a dose-dependent manner. Further results indicated that YF-18 inhibited cell proliferation and migration through down-regulating Skp2 and up-regulating its substrates, p27 and E-cadherin. Moreover, YF-18 inhibited A549-luciferase cell xenograft tumor growth in a dose-dependent manner. The findings indicate that YF-18 bears therapeutic potentials for lung cancer.

Keywords: Skp2; lung cancer; matrine derivative; migration; proliferation.

MeSH terms

  • A549 Cells
  • Alkaloids / chemistry
  • Alkaloids / pharmacology*
  • Animals
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Down-Regulation
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / pathology
  • Matrines
  • Quinolizines / chemistry
  • Quinolizines / pharmacology*
  • Random Allocation
  • S-Phase Kinase-Associated Proteins / metabolism*

Substances

  • Alkaloids
  • Quinolizines
  • S-Phase Kinase-Associated Proteins
  • Matrines