title: Plasmid-based Survivin shRNA and GRIM-19 carried by attenuated Salmonella suppresses tumor cell growth.
abstract: 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.
authors.affiliation: Prostate Diseases Prevention and Treatment Research Centre and Department of Pathophysiology, Norman Bethune Medical School, Jilin University, Changchun130021, China.
authors.forename: Yan-Bo
authors.initials: YB
authors.lastname: Liu
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Ya-Xiong
authors.initials: YX
authors.lastname: Guo
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: Gao
authors.forename: Xi-Chun
authors.initials: XC
authors.lastname: Liu
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Zhao
authors.forename: Bao-Feng
authors.initials: BF
authors.lastname: Guo
authors.forename: Li-Jing
authors.initials: LJ
authors.lastname: Zhao
authors.forename: Xue-Jian
authors.initials: XJ
authors.lastname: Zhao
authors.forename: De-Qi
authors.initials: DQ
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism / Q000628:therapy*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000378:metabolism; D015870:Gene Expression; D015316:Genetic Therapy; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids; D011467:Prostate / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000628:therapy*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism / Q000627:therapeutic use*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012486:Salmonella typhimurium; D000077022:Survivin; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C494811:BCL2L1 protein, human; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000077022:Survivin; D042461:Vascular Endothelial Growth Factor A; D051020:bcl-X Protein; D019938:Cyclin D1; D009247:NADH, NADPH Oxidoreductases; C439057:NDUFA13 protein, human; D053148:Caspase 3