Using attenuated Salmonella typhi as tumor targeting vector for MDR1 siRNA delivery

Area of Science:

• Oncology
• Molecular Biology
• Bacteriology

Background:

• Multidrug resistance (MDR) is a major challenge in cancer therapy.
• Small interference RNA (siRNA) offers potential for targeted gene silencing.
• Effective in vivo delivery of siRNA to solid tumors remains a significant hurdle.

Purpose of the Study:

• To evaluate attenuated Salmonella typhi as a delivery vector for MDR1 siRNA.
• To assess the feasibility of this approach in a human tongue squamous cell cancer mouse model.
• To explore a novel in vivo administration route for siRNA against malignant tumors.

Main Methods:

• Established a cisplatin-resistant tongue cancer cell line (Tca8113/DDP) overexpressing MDR1.
• Constructed a plasmid expressing MDR1 siRNA and transformed it into attenuated Salmonella typhi.
• Infected cancer cells in vitro and administered recombinant Salmonella orally to tumor-bearing mice treated with cisplatin.

Main Results:

• Recombinant Salmonella successfully infected Tca8113/DDP cells, suppressing P-glycoprotein expression and reversing cisplatin tolerance.
• Oral administration of recombinant Salmonella in mice suppressed tumor proliferation.
• The combination therapy enhanced the therapeutic effect of cisplatin.

Conclusions:

• Attenuated Salmonella typhi demonstrates potential as an in vivo delivery vector for siRNA.
• This strategy can target siRNA to tumor tissues for cancer treatment.
• The approach shows promise for overcoming multidrug resistance in cancer therapy.