lasmid-based Survivin shRNA and GRIM-19 carried by attenuated Salmonella suppresses tumor cell growth

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） ca...

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Published in:亚洲男性学杂志：英文版 2012, Vol.14 (4), p.536-545
Main Author: Yan-Bo Liu Ling Zhang Ya-Xiong Guo Li-Fang Gao Xi-Chun Liu Li-Juan Zhao Bao-Feng Guo Li-Jing Zhao Xue-Jian Zhao De-Qi Xu
Format: Article
Language:English
Subjects:
RNA干扰
shRNA
Survivin
减毒沙门氏菌
生长抑制
肿瘤细胞
鼠伤寒沙门氏菌
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Summary: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 vitroand in vivo. This study has provided a novel cancer gene therapeutic approach for prostate cancer.
ISSN:1008-682X
1745-7262