文献类型：期刊文献

英文题名：Adeno-associated virus-delivered short hairpin-structured RNA for androgen receptor gene silencing induces tumor eradication of prostate cancer xenografts in nude mice: a preclinical study

作者：Sun, Aijing[1,2];Tang, Jianxi[3];Terranova, Paul F.[4];Zhang, Xiaoming[5];Thrasher, James Brantley[3];Li, Benyi[1,2,3,4]

机构：[1]Shaoxing Univ, Affiliated Hosp 1, Shaoxing, Zhejiang, Peoples R China;[2]Shaoxing Peoples Hosp, Dept Pathol, Shaoxing, Zhejiang, Peoples R China;[3]Univ Kansas, Med Ctr, Dept Urol, Kansas City, KS 66103 USA;[4]Univ Kansas, Med Ctr, Dept Mol & Integrated Physiol, Kansas City, KS 66103 USA;[5]Univ Kansas, Med Ctr, Dept Anat & Cell Biol, Kansas City, KS 66103 USA

年份：2010

卷号：126

期号：3

起止页码：764

外文期刊名：INTERNATIONAL JOURNAL OF CANCER

收录：SCI-EXPANDED(收录号：WOS:000273515500018)、、Scopus(收录号：2-s2.0-73449116411)、WOS

基金：Department of Defense PCRP; Grant numbers: W81XWH-04-1-0214, W81XWH-07-1-0021; Grant sponsor: Zhejiang Provincial Natural Science Foundation of China; Grant number: Y206078; Grant sponsors: KU William L. Valk Endowment, Kansas Mason's Foundation, SWOG HOPE Foundation, The University of Kansas Medical Center (KIUMC)

语种：英文

外文关键词：prostate cancer; androgen receptor; short-hairpin RNA; adeno-associated virus; nude mice xenograft

外文摘要：The androgen receptor (AR) is the most critical factor in prostate cancer progression. We previously demonstrated that silencing the AR using 2 unique small interfering RNAs (no. 8 and no. 31 AR siRNA) induces apoptotic cell death in AR-positive prostate cancer cells. To develop this AR siRNA technique into a therapy for prostate cancers, we generated an adeno-associated virus (AAV) vector to stably express a short hairpin-structured RNA (shRNA) against the AR gene in vivo. In addition to the no. 8 AR shRNA (ARHP8), we also screened a group of AR shRNAs with different sequences and identified a less effective AR shRNA (ARHP4) that was used as an shRNA control. An empty AAV vector (AAV-GFP) was used as a negative control. Intratumoral injection of AAV-ARHP8 viruses significantly suppressed tumor growth of xenografts derived from either androgen-responsive or castration-resistant prostate cancer cells. Most interestingly, systemic delivery of the AAV-ARHP8 but not AAV-ARHP4 or AAV-GFP viruses via tail vein injection eliminated xenografts within 10 days. Further analysis revealed that AAV-ARHP8 viruses dramatically reduced the expression of AR-regulated cellular survival genes and caused a dramatic apoptotic response. Taken together, our data strongly suggest that AAV-ARHP8 viruses induced a strong AR gene silencing in vivo and that systemic delivery of ARHP8 siRNA via an AAV vector or any other means might be considered as novel gene therapy for prostate cancers.