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

摘要

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.