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Updated: May 22, 2026
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Targeted therapy via oral administration of attenuated Salmonella expression plasmid-vectored Stat3-shRNA cures
1Prostate Diseases Prevention and Treatment Research Centre and Department of Pathophysiology, Norman Bethune College of Medicine, Jilin University, Changchun, People's Republic of China.
Abstract:
The development of RNA interference-based cancer gene therapies has been delayed due to the lack of effective tumor-targeting delivery systems. Attenuated Salmonella enterica serovar Typhimurium (S. Typhimurium) has a natural tropism for solid tumors. We report here the use of attenuated S. Typhimurium as a vector to deliver shRNA directly into tumor cells. Constitutively activated signal transducer and activator of transcription 3 (Stat3) is a key transcription factor involved in both hepatocellular carcinoma (HCC) growth and metastasis. In this study, attenuated S. Typhimurium was capable of delivering shRNA-expressing vectors to the targeted cancer cells and inducing RNA interference in vivo. More importantly, a single oral dose of attenuated S. Typhimurium carrying shRNA-expressing vectors targeting Stat3 induced remarkably delayed and reduced HCC (in 70% of mice). Cancer in these cured mice did not recur over 2 years following treatment. These data demonstrated that RNA interference combined with Salmonella as a delivery system may offer a novel clinical approach for cancer gene therapy.
Insights
Researchers used Salmonella bacteria to deliver cancer-fighting RNA interference (RNAi) directly to tumor cells. This novel approach successfully reduced hepatocellular carcinoma (HCC) in mice, offering a promising new cancer gene therapy strategy.
Area of Science:
- Oncology
- Microbiology
- Gene Therapy
Background:
- Effective tumor-targeting delivery systems are crucial for RNA interference (RNAi) cancer gene therapies.
- Attenuated Salmonella enterica serovar Typhimurium (S. Typhimurium) exhibits natural tropism for solid tumors, making it a potential delivery vector.
Purpose of the Study:
- To investigate the use of attenuated S. Typhimurium as a vector for delivering short hairpin RNA (shRNA) directly into tumor cells for cancer gene therapy.
- To evaluate the efficacy of S. Typhimurium-mediated delivery of shRNA targeting Signal Transducer and Activator of Transcription 3 (Stat3) in hepatocellular carcinoma (HCC).
Main Methods:
- Utilized attenuated S. Typhimurium to deliver shRNA-expressing vectors targeting Stat3 into cancer cells.
- Administered a single oral dose of the engineered S. Typhimurium to mice with HCC.
- Monitored tumor growth, metastasis, and recurrence over a 2-year period.
Main Results:
- Attenuated S. Typhimurium successfully delivered shRNA-expressing vectors to targeted cancer cells, inducing RNA interference in vivo.
- A single oral dose of S. Typhimurium carrying Stat3-targeting shRNA resulted in significantly delayed and reduced HCC in 70% of treated mice.
- No cancer recurrence was observed in the cured mice over the 2-year follow-up period.
Conclusions:
- RNA interference combined with Salmonella as a delivery system represents a novel and potentially effective clinical approach for cancer gene therapy.
- This strategy shows promise for treating hepatocellular carcinoma and potentially other solid tumors.
