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

Silvia Monteagudo, Francisco C Pérez-Martínez, María D Pérez-Carrión, Javier Guerra, Sonia Merino, María Prado Sánchez-Verdú, Valentín Ceña

NanoDrugs, S.L. Parque Científico y Tecnológico, Albacete, Spain.

Nanomedicine (London, England) 2012 Apr

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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. 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. 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. 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.

Citation

Silvia Monteagudo, Francisco C Pérez-Martínez, María D Pérez-Carrión, Javier Guerra, Sonia Merino, María Prado Sánchez-Verdú, Valentín Ceña. Inhibition of p42 MAPK using a nonviral vector-delivered siRNA potentiates the anti-tumor effect of metformin in prostate cancer cells. Nanomedicine (London, England). 2012 Apr;7(4):493-506