Using attenuated Salmonella typhi as tumor targeting vector for MDR1 siRNA delivery.
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.
Jiang
Zhongming
Z
Department of Stomatology; Changhai Hospital, Second Military Medical University, Shanghai, China. jiangzhongming-s@163.com
Zhao
Ping
P
Zhou
Zhonghua
Z
Liu
Jun
J
Qin
Liying
L
Wang
Hongwei
H
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
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; D002945:Cisplatin