Inhibition of p42 MAPK using a nonviral vector-delivered siRNA potentiates the anti-tumor effect of metformin in prostate cancer cells

Nanomedicine (Lond). 2012 Apr;7(4):493-506. doi: 10.2217/nnm.11.61. Epub 2011 Oct 13.

Abstract

Aims: The aim of this work was to study if a G1-polyamidoamine dendrimer/siRNA dendriplex can remove the p42 MAPK protein in prostate cancer cells and to potentiate the anti-tumoral effect of the antidiabetic drug metformin and taxane docetaxel.

Material & methods: The dendriplex uptake was studied using flow cytometry analysis. Transfection efficiency was determined by measuring p42 MAPK mRNA and protein levels. Anti-tumoral effects were determined by measuring cellular proliferation and damage.

Results: The dendriplex siRNA/G1-polyamidoamine dendrimer decreased both p42 MAPK mRNA and protein levels by more than 80%, which potentiates the anti-tumoral effects of metformin.

Conclusion: Blockade of the MAPK pathway using a dendrimer-vehiculized siRNA to block the MAPK signaling pathway in prostate cancer cells can potentiate the anti-tumoral activity of anticancer drugs, indicating that the combination of siRNA-mediated blockade of survival signals plus anti-tumoral therapy might be a useful approach for cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Blotting, Western
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Flow Cytometry
  • Humans
  • Hydro-Lyases / metabolism
  • Male
  • Metformin / pharmacology*
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • RNA, Small Interfering / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects

Substances

  • RNA, Small Interfering
  • Metformin
  • Mitogen-Activated Protein Kinase 1
  • Caspase 3
  • Hydro-Lyases
  • lactate dehydratase