title: Intratumoral delivery and suppression of prostate tumor growth by attenuated Salmonella enterica serovar typhimurium carrying plasmid-based small interfering RNAs.
abstract: The facultative anaerobic, invasive Salmonella enterica serovar typhimurium (S. typhimurium) has been shown to retard the growth of established tumors. We wondered if a more effective antitumor response could be achieved in vivo if these bacteria were used as tools for delivering specific molecular antitumor therapeutics. Constitutively activated transcription factor signal transducer and activator of transcription 3 (STAT3) promotes the survival of a number of human tumors. In this study, we investigated the relative efficacies of attenuated S. typhimurium alone or combined with Stat3-specific small interfering RNA (siRNA) in terms of tumor growth and metastasis. The bacteria preferentially homed into tumors over normal liver and spleen tissues in vivo. S. typhimurium expressing plasmid-based Stat3-specific siRNAs significantly inhibited tumor growth, reduced the number of metastastic organs, and extended the life time for C57BL6 mice bearing an implanted prostate tumor, versus bacterial treatment alone. These results suggest that attenuated S. typhimurium combined with an RNA interference approach might be more effective for the treatment of primary as well as metastatic cancer.
authors.affiliation: Prostate Diseases Prevention and Treatment Research Centre and Department of Pathophysiology, School of Basic Medicine, Jilin University, Changchun, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Lifang
authors.initials: L
authors.lastname: Gao
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhao
authors.forename: Baofeng
authors.initials: B
authors.lastname: Guo
authors.forename: Kun
authors.initials: K
authors.lastname: Ji
authors.forename: Yong
authors.initials: Y
authors.lastname: Tian
authors.forename: Jinguo
authors.initials: J
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.forename: Jiadi
authors.initials: J
authors.lastname: Hu
authors.forename: Dhananjaya V
authors.initials: DV
authors.lastname: Kalvakolanu
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Kopecko
authors.forename: Xuejian
authors.initials: X
authors.lastname: Zhao
authors.forename: De-Qi
authors.initials: DQ
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis; D015152:Blotting, Northern; D015153:Blotting, Western; D049109:Cell Proliferation; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids; D011471:Prostatic Neoplasms / Q000382:microbiology / Q000628:therapy*; D034622:RNA Interference; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor / Q000235:genetics*; D012486:Salmonella typhimurium
chemical_list: D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor