Combinational RNAi gene therapy of hepatocellular carcinoma by targeting human EGFR and TERT

【作者】 Yurong Hu,Yingying Shen,Baofang Ji,Lei Wang,Zhenzhong Zhang*,YunZhang

【期刊名】 European Journal of Pharmaceutical Sciences

【影响因子】 2011年:3.212

【作者单位】 Zhengzhou Univ, Sch Pharm, 100 Sci Rd, Zhengzhou 450001, Henan, Peoples R China

【年，卷(期)：页码】2011.3.18,42(4):387-391

【关键词】 EGFR; TERT; Combinationalgenetherapy; RNA interference; Pegylated immuno-lipopolyplexes

【摘要】Both human telomerase reverse transcriptase (hTERT) and epidermal growth factor receptor (hEGFR) are ideal targets for RNA interference (RNAi)-based genetherapyofhepatocellularcarcinoma. Two shRNA expression plasmids pU6-shTERT and pU6-shEGFR targeting hTERT and hEGFR, respectively, were separately formulated as pegylated immuno-lipopolyplexes, a novel non-viral gene delivery system. In vitro studies showed that when pU6-shTERT and pU6-shEGFR were combined and applied to SMMC-7721 cells, there was a significant additive effect on cytotoxicity as well as cell apoptosis, compared to pU6-shTERT or pU6-shEGFR alone, with a cell viability of 50.9 +/- 7.4%, 79.2 +/- 3.6% and 77.1 +/- 3.6%, respectively, and with a cell apoptotic rate of 44.8 +/- 0.9%, 25.1 +/- 0.4% and 29.5 +/- 0.8%, respectively. In vivo study in SMMC-7721 xenograft tumor model demonstrated that intravenous administration of PILP-formulated pU6-shTERT and pU6-shEGFR caused an additive effect on tumor growth inhibition, compared to pU6-shTERT or pU6-shEGFR alone, with a tumor growth inhibition rate of 74.0%, 36.3% and 46.1%, respectively, which is consistent with the downregulated EGFR and TERT mRNA expression. The results suggest that combinationalRNAigenetherapyofhepatocellularcarcinomabytargetinghumanEGFR and TERT with pegylated immuno-lipopolyplexes is a new and good strategy. (C) 2011 Elsevier B.V. All rights reserved.

窗体底端

tumor-targeting property, NIR laser-controlled drug releasing function and X-ray imaging ability, demonstrating that there is a great potential of GO@Ag-DOX-NGR for cancer diagnosis and therapy.

【全文链接】http://www.sciencedirect.com/science/article/pii/S092809871100008