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Volume 14, Issue 4 (July 2012) 14, 536–545; 10.1038/aja.2011.179
Plasmid-based Survivin shRNA and GRIM-19 carried by attenuated Salmonella suppresses tumor cell growth
Yanbo Liu1,2,*, Ling Zhang1,*, Yaxiong Guo1, Lifang Gao1, Xichun Liu1, Lijuan Zhao1, Baofeng Guo1, Lijing Zhao1, Xuejian Zhao1,3 and Deqi Xu4
1 Prostate Diseases Prevention and Treatment Research Centre and Department of Pathophysiology, Norman Bethune Medical School, Jilin University, Changchun 130021, China
2 Department of Pathophysiology, School of Bacic Medicine, Beihua University, Jilin 132013, China
3 Urology center, The First Hospital of Jilin University, Changchun 130021, China
4 New Vaccine National Engineering Research Center, Beijing 100176, China
* These authors contributed equally to this work.
Correspondence: Dr XJ Zhao (zhaoxuejian2007@yahoo.com.cn) and Dr DQ Xu (dqxujl@gmail.com)
Received: 10 September 2011; Revised: 6 November 2011; Accepted: 1 December 2011; Published online: 14 May 2012
| Abstract |
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Persistent activation of Survivin and its overexpression contribute to the formation, progression and metastasis of several different
tumor types. Therefore, Survivin is an ideal target for RNA interference mediated-growth inhibition. Blockade of Survivin using specific short hairpin RNAs (shRNA) can significantly reduce prostate tumor growth. RNA interference does not fully ablate target gene
expression, owing to the idiosyncrasies associated with shRNAs and their targets. To enhance the therapeutic efficacy of Survivin-specific shRNA, we employed a combinatorial expression of Survivin-specific shRNA and gene associated with retinoid-interferon-induced mortality-19 (GRIM-19). Then, the GRIM-19 coding sequences and Survivin-specific shRNAs were used to create a dual expression plasmid vector and were carried by an attenuated strain of Salmonella enteric serovar typhimurium (S. typhimurium) to treat prostate cancer in vitro and in vivo. We found that the co-expressed Survivin-specific shRNA and GRIM-19 synergistically and more effectively inhibited prostate tumor proliferation and survival, when compared with treatment with either single agent alone in vitro and in vivo. This study has provided a novel cancer gene therapeutic approach for prostate cancer.
Keywords: GRIM-19; prostate cancer; RNAi; Salmonella enterica serovar typhimurium; Survivin; tumor cell growth
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