NanoDrugs, S.L. Parque Científico y Tecnológico, Albacete, Spain.
Nanomedicine (Lond). 2012 Apr;7(4):493-506. doi: 10.2217/nnm.11.61. Epub 2011 Oct 13.
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.
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.
本研究旨在探讨 G1-聚酰胺-胺树枝状大分子/RNA 树枝状聚合物能否去除前列腺癌细胞中的 p42 MAPK 蛋白，并增强抗糖尿病药物二甲双胍和紫杉烷类药物多西紫杉醇的抗肿瘤作用。
采用流式细胞术分析研究树枝状聚合物的摄取情况。通过测量 p42 MAPK mRNA 和蛋白水平来确定转染效率。通过测量细胞增殖和损伤来确定抗肿瘤效果。
siRNA/G1-聚酰胺-胺树枝状大分子复合物使 p42 MAPK mRNA 和蛋白水平降低超过 80%，从而增强了二甲双胍的抗肿瘤作用。
使用树枝状聚合物载体 RNA 来阻断 MAPK 信号通路，从而抑制前列腺癌细胞中的 MAPK 信号通路，可增强抗肿瘤药物的抗肿瘤活性，这表明 RNA 介导的阻断生存信号与抗肿瘤治疗相结合可能是癌症治疗的一种有效方法。
