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. CONCLUSION: Attenuated Salmonella typhi is expected to act as an in vivo targeting delivery vector for siRNA in tumor tissues.