ERK1/2 promoted proliferation and inhibited apoptosis of human cervical cancer cells and regulated the expression of c-Fos and c-Jun proteins

Med Oncol. 2015 Mar;32(3):57. doi: 10.1007/s12032-015-0490-5. Epub 2015 Feb 3.

Abstract

Small-molecule inhibitors targeted MAPK have been wildly used for some cancer therapeutics as a biologically viable model, but no one has been used for cervical caner. ERK1/2, one of MAPK kinases, is expressed high in cervical cancer tissue. The aim of the present study was to evaluate the effects of ERK1/2 inhibitor U0126 on proliferation and apoptosis of cervical cancer cells and appraise the correlated mechanism of the effects. In this study, the cell proliferation of Hela and C33A cervical cancer cells was tested by Cell Counting Kit-8 (CCK8) assay and cell counting after treated with ERK1/2 inhibitor U0126. The cell cycle and apoptosis were evaluated by flow cytometry (FCM). The protein levels of ERK1/2 and c-Fos and c-Jun were detected by Western blot. The results indicated that after down-regulating ERK1/2 proteins with the inhibitor U0126, Hela and C33A cells proliferation was inhibited, cell apoptosis was promoted, the proportions of G0/G1 stage in cell cycle increased, and G2/M stages decreased. After down-regulating ERK1/2 proteins of Hela and C33A cells, the expression levels of p-c-Fos protein decreased, while p-c-Jun protein increased. The results of this study indicated that ERK1/2 may promote the development of cervical cancer cells, suggesting ERK1/2 inhibitor may be used as an effective target for cervical cancer therapies working for. It might inhibit cervical cancer cells growth via regulating the transcription factors expression of c-Fos and c-Jun.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Butadienes / pharmacology
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Female
  • HeLa Cells / drug effects
  • Humans
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Nitriles / pharmacology
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Proto-Oncogene Proteins c-jun / metabolism*
  • Uterine Cervical Neoplasms / drug therapy
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology*

Substances

  • Butadienes
  • Enzyme Inhibitors
  • Nitriles
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • U 0126
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3