Intratumoral delivery and suppression of prostate tumor growth by attenuated Salmonella enterica serovar typhimurium carrying plasmid-based small interfering RNAs.
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.
Zhang
Ling
L
Prostate Diseases Prevention and Treatment Research Centre and Department of Pathophysiology, School of Basic Medicine, Jilin University, Changchun, P.R. China.
Gao
Lifang
L
Zhao
Lijuan
L
Guo
Baofeng
B
Ji
Kun
K
Tian
Yong
Y
Wang
Jinguo
J
Yu
Hao
H
Hu
Jiadi
J
Kalvakolanu
Dhananjaya V
DV
Kopecko
Dennis J
DJ
Zhao
Xuejian
X
Xu
De-Qi
DQ
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
D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor