title: Delivery of the co-expression plasmid pEndo-Si-Stat3 by attenuated Salmonella serovar typhimurium for prostate cancer treatment.
abstract: OBJECTIVE
  To investigate the therapeutic utility of an attenuated bacterium carrying a plasmid that co-expresses Endostatin, an inhibitor of tumor neovasculogenesis, and a shRNA that targets Stat3 to suppress prostate cancer growth.
  
  
  METHODS
  Plasmid pEndo-Si-Stat3 was constructed and introduced into an attenuated strain of Salmonella enterica serovar typhimurium. The resultant recombinant bacterium was used as a vector to deliver the plasmid to tumor cells growing in vivo. Tumor-associated gene and protein expression changes were measured by using RT-PCR and Western blot analyses. Expression of Endostatin in tumor tissue was detected by ELISA. The presence of vector bacteria in tissues was monitored and tumor destruction was assessed by using TUNEL and H&E staining assays.
  
  
  RESULTS
  Bacterially delivered pEndo-Si-Stat3 decreased Stat3 levels and increased Endostatin expression in mouse tumors, resulting in a significant suppression of tumor growth (P < 0.01). Expression of Bcl-2 and PCNA was down-regulated and Caspase3 expression was up-regulated to promote apoptosis of tumor cells.
  
  
  CONCLUSIONS
  Successful delivery by attenuated Salmonella of the combination therapeutic plasmid simultaneously knocked down the expression of Stat3 and resulted in over-expression of Endostatin, which synergistically inhibited prostate cancer growth.
authors: Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Center, Norman Bethune Medical School, Jilin University, Xinmin Street, Changchun, 130021, People's Republic of China.
authors: Xin
authors: X
authors: Li
authors: Yang
authors: Y
authors: Li
authors: Bo
authors: B
authors: Wang
authors: Kun
authors: K
authors: Ji
authors: Zuowen
authors: Z
authors: Liang
authors: Baofeng
authors: B
authors: Guo
authors: Jiadi
authors: J
authors: Hu
authors: Di
authors: D
authors: Yin
authors: Yanwei
authors: Y
authors: Du
authors: Dennis J
authors: DJ
authors: Kopecko
authors: Dhananjaya V
authors: DV
authors: Kalvakolanu
authors: Xuejian
authors: X
authors: Zhao
authors: Deqi
authors: D
authors: Xu
authors: Ling
authors: L
authors: Zhang
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D043169:Endostatins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D012486:Salmonella typhimurium / Q000235:genetics; D013997:Time Factors; D047368:Tumor Burden / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D043169:Endostatins; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D042461:Vascular Endothelial Growth Factor A