Metapristone suppresses non-small cell lung cancer proliferation and metastasis via modulating RAS/RAF/MEK/MAPK signaling pathway

Biomed Pharmacother. 2017 Jun:90:437-445. doi: 10.1016/j.biopha.2017.03.091. Epub 2017 Apr 6.

Abstract

Background: Metastasis is the key phase of cancer progression that characterizes a more advanced stage and a poorer prognosis. The majority of cancer fatalities occur as a consequence of metastasis.

Objective: Mifepristone (RU486), a chemical abortifacient, has recently been used in clinical trials for psychotic depression and cancer chemotherapy. As the most predominant biological active metabolite of mifepristone, metapristone is being developed as a novel cancer metastasis chemopreventive agent by us. However, there is no information available to address the effects of metapristone on non-small cell lung cancer (NSCLC). The aim of our study was to investigate the inhibitory effect of metapristone on the proliferation and metastasis of NSCLC cells.

Method: In the present study, we evaluated the efficacy of metapristone on the growth, migration and invasion in different kinds of NSCLC cells (A549, H1975 and H1299), and further investigated the underlying mechanism of metapristone by real time PCR and western blot assay.

Results: Metapristone could significantly inhibit the proliferation, migration and invasion of NSCLC cells through suppressing RAS/RAF/MEK/MAPK and PI3K/AKT signaling pathways. Moreover, metapristone could effectively inhibit the formation of NSCLC cells' cytoskeleton in a concentration-dependent manner, which possibly led to the inhibition of NSCLC cells' migration.

Conclusion: Overall, it was preliminarily demonstrated that metapristone could be developed as a useful agent to show anti-metastasis activity for NSCLC.

Keywords: Invasion; Metapristone; Metastasis; Migration; Non-small cell lung cancer; Proliferation.

MeSH terms

  • A549 Cells
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • MAP Kinase Signaling System / drug effects
  • Mifepristone / analogs & derivatives*
  • Mifepristone / pharmacology
  • Mitogen-Activated Protein Kinases / metabolism
  • Neoplasm Metastasis / drug therapy*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • Signal Transduction / drug effects*
  • raf Kinases / metabolism

Substances

  • Mifepristone
  • Phosphatidylinositol 3-Kinases
  • raf Kinases
  • Mitogen-Activated Protein Kinases
  • Proto-Oncogene Proteins p21(ras)
  • metapristone