Dendrimers-delivered short hairpin RNA targeting hTERT inhibits oral cancer cell growth in vitro and in vivo

被引:35
|
作者
Liu, Xiqiang [1 ,2 ]
Huang, Hongzhang [1 ,2 ]
Wang, Jianguang [3 ]
Wang, Cheng [1 ,2 ]
Wang, Miao [1 ,2 ]
Zhang, Bin [3 ]
Pan, Chaobin [3 ]
机构
[1] Sun Yat Sen Univ, Dept Oral & Maxillofacial Surg, Guanghua Sch Stomatol, Guangzhou 510055, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Inst Stomatol Res, Guangzhou 510055, Guangdong, Peoples R China
[3] Sun Yat Sen Univ, Dept Oral & Maxillofacial Surg, Affiliated Hosp 2, Guangzhou 510120, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
Human telomerase reverse transcriptase; Dendrimer; Gene delivery; Oral cancer; RNA interference; TELOMERASE REVERSE-TRANSCRIPTASE; PAMAM DENDRIMERS; SIRNA DELIVERY; EXPRESSION; APOPTOSIS; GENE; CARCINOGENESIS; PATHWAY; ACTIVATION; DEATH;
D O I
10.1016/j.bcp.2011.03.017
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Promising therapeutic application of RNA interference (RNAi) depends on the availability of safe and efficient intracellular delivery systems. Human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase complex, is an attractive therapeutic target for oral cancer. Here we investigated the characteristics and anticancer effect of polyamidoamine (PAMAM) dendrimer-mediated short hairpin RNA (shRNA) against hTERT in oral cancer. Dendrimer-mediated shRNA efficiently silenced the hTERT gene in vitro, resulted in cell growth inhibition and apoptosis. Treatment with the shRNA dendriplex attenuated tumor growth in a xenograft model. These studies suggest that RNAi-mediated hTERT gene silencing, coupled with dendrimer delivery, may provide a promising approach for the treatment of oral cancer, in which hTERT is abundantly expressed. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:17 / 23
页数:7
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