期刊
NANOMEDICINE
卷 7, 期 4, 页码 493-506出版社
FUTURE MEDICINE LTD
DOI: 10.2217/NNM.11.61
关键词
caspase 3; cell death; dendrimer; docetaxel; drug delivery; metformin; p42MAPK; PAMAM; prostate cancer; siRNA
资金
- Ministerio de Ciencia e Innovacion (Spain)
- NanoDrugs, S.L., Spain
- Fondo de Investigaciones Sanitarias [PI081434]
- Consejeria de Educacion, JCCM [PII1I0909-0163-4002, POII10-0274-3182]
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.
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