Inhibition of p42 MAPK using a nonviral vector-delivered siRNA potentiates the anti-tumor effect of metformin in prostate cancer cells. (April 2012)

• Record Type: Journal Article
• Authors: Monteagudo, Silvia; Pérez-Martínez, Francisco C; Pérez-Carrión, María D; Guerra, Javier; Merino, Sonia; Sánchez-Verdú, María Prado; Ceña, Valentín
• Is Part Of: Nanomedicine. Volume 7:Number 4(2012)
• Page Start: 493
• Page End: 506
• Publication Date: 2012-04
• Subjects: caspase 3 -- cell death -- dendrimer -- docetaxel -- drug delivery -- metformin -- p42MAPK -- PAMAM -- prostate cancer -- siRNA; Nanotechnology -- Periodicals; Medical technology -- Periodicals; Nanotechnology -- Therapeutic use -- Periodicals; 610.28
• DOI: 10.2217/nnm.11.61
• Languages: English
• ISSNs: 1743-5889

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.