title: Using attenuated Salmonella typhi as tumor targeting vector for MDR1 siRNA delivery.
abstract: OBJECTIVE
  To investigate the feasibility of using attenuated Salmonella typhi as an in vivo delivery vector for multidrug-resistance gene (MDR1) small interference RNA (siRNA) in a mouse model bearing human tongue squamous cell cancer. This technique may represent a novel and effective route for the in vivo administration of siRNA against malignant tumors.
  
  
  METHODS
  The cisplatin (DDP)-resistant human tongue squamous cell carcinoma cell line Tca8113/DDP, which highly expresses the MDR1 gene, was established by exposure to gradually increasing concentrations of cisplatin. A plasmid MDR1 siRNAwas constructed and transformed into attenuated Salmonella typhi strain SL7207. Tca8113/ DDP cells were infected with recombinant salmonella and expression of the MDR1 gene encoding P-glycoprotein (P-gp) product was detected. Tca8113/DDP tumor-bearing nude mice were established by inoculation by gavage administration of recombinant salmonella and were simultaneously injected intraperitoneally with cisplatin. Tumor growth was observed.
  
  
  RESULTS
  Recombinant salmonella-bearing MDR1 siRNA expression plasmids can infect Tca8113/DDP cells in vitro and suppress P-gp expression and reverse DDP tolerance in Tca8113/DDP cells. Oral administration of recombinant salmonella in tumor-bearing nude mice can suppress tumor proliferation and enhance the therapeutic effect of DDP.
  
  
  CONCLUSIONS
  Attenuated Salmonella typhi is expected to act as an in vivo targeting delivery vector for siRNA in tumor tissues.
authors: Department of Stomatology; Changhai Hospital, Second Military Medical University, Shanghai, China. jiangzhongming-s@163.com
authors: Zhongming
authors: Z
authors: Jiang
authors: Ping
authors: P
authors: Zhao
authors: Zhonghua
authors: Z
authors: Zhou
authors: Jun
authors: J
authors: Liu
authors: Liying
authors: L
authors: Qin
authors: Hongwei
authors: H
authors: Wang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D018307:Neoplasms, Squamous Cell / Q000188:drug therapy / Q000382:microbiology / Q000628:therapy*; D010957:Plasmids / Q000235:genetics; D034741:RNA, Small Interfering / Q000627:therapeutic use*; D012485:Salmonella typhi / Q000235:genetics*; D014062:Tongue Neoplasms / Q000188:drug therapy / Q000382:microbiology / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; D002945:Cisplatin