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Updated: Apr 1, 2026
Bioluminescence Imaging of an Immunocompetent Animal Model for Glioblastoma
Published on: January 15, 2016
The engineered Salmonella typhimurium inhibits tumorigenesis in advanced glioma
Jian-Qiang Chen1, Yue-Fu Zhan2, Wei Wang1
1Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha, People's Republic of China.
Objective:
To explore the antitumor role of the attenuated Salmonella typhimurium ΔppGpp with inducible cytolysin A (ClyA) in advanced stage of glioma.
Materials And Methods:
The C6 rat glioma cells were orthotopically implanted by surgery into the caudate nucleus of rat brains. The rats were then randomly divided into the treatment group (SL + ClyA) (n=12), negative control group (SL) (n=12), and control group (phosphate-buffered saline [PBS]) (n=12). In the treatment group, the attenuated S. typhimurium were transformed with the plasmid-encoded antitumor gene ClyA. The expression of ClyA was controlled by the TetR-regulated promoter in response to extracellular doxycycline. The plasmid also contained an imaging gene lux to allow illumination of the tumor infected by the bacteria. The rat glioma C6 cells were implanted into the caudate nucleus of all rats. The engineered S. typhimurium and respective controls were injected intravenously into the rats 21 days after initial tumor implantation. The pathological analysis of the glioma tumor was performed at 21 days and 28 days (7 days after doxycycline treatment) postimplantation. All rats underwent MRI (magnetic resonance imaging) and bioluminescence study at 21 days and 28 days postimplantation to detect tumor volume. The differences between the three groups in tumor volume and survival time were analyzed.
Results:
Advanced stage glioma was detected at 21 days postimplantation. Bioluminescence showed that the engineered S. typhimurium accumulated in glioma tumors and disappeared in the normal reticuloendothelial tissues 3 days after intravenous injection. MRI showed that the tumor volume in the S. typhimurium with ClyA group were significantly reduced compared to the bacteria alone and no bacteria groups 7 days post-doxycycline treatment (P<0.05), while the necrotic tumor volume in the S. typhimurium with ClyA group and S. typhimurium alone group increased significantly compared to the control group (P<0.01). In addition, the survival time was significantly prolonged in the bacteria-treated group compared to the PBS-treated control group (P<0.01).
Conclusion:
The engineered S. typhimurium can significantly induce cancer cell apoptosis in the tumor center and inhibit cancer cell proliferation in the outer zone of advanced glioma tumor, leading to a prolonged survival time in rats. In addition, the engineered S. typhimurium that carried the antitumor and imaging genes controlled by the TetR-regulated promoter have high delivery efficiency with tolerable side effects in rats.
Insights
Engineered Salmonella typhimurium carrying the cytolysin A gene effectively reduced glioma tumor volume and prolonged survival time in rats. This innovative approach shows promise for advanced glioma treatment.
Area of Science:
- Oncology
- Microbiology
- Biotechnology
Background:
- Advanced glioma presents significant treatment challenges.
- Targeted bacterial therapies offer a novel approach to cancer treatment.
Purpose of the Study:
- To investigate the antitumor efficacy of attenuated Salmonella typhimurium (S. typhimurium) engineered with inducible cytolysin A (ClyA) in advanced glioma.
- To evaluate the impact of this engineered bacteria on tumor volume and survival rates in a rat model.
Main Methods:
- Orthotopic C6 rat glioma model established.
- Rats treated with engineered S. typhimurium (SL + ClyA), S. typhimurium alone (SL), or PBS.
- Bioluminescence and MRI used for tumor detection and volume measurement.
- Pathological analysis and survival time assessment performed.
Main Results:
- Engineered S. typhimurium selectively accumulated in glioma tumors.
- Significant reduction in tumor volume observed in the S. typhimurium with ClyA group post-doxycycline treatment (P<0.05).
- Increased necrotic tumor volume and prolonged survival time in bacteria-treated groups compared to controls (P<0.01).
Conclusions:
- Engineered S. typhimurium effectively induces apoptosis and inhibits proliferation in advanced glioma.
- This therapy demonstrates high delivery efficiency and tolerable side effects.
- The TetR-regulated promoter system allows controlled expression of antitumor and imaging genes.
