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Genetically-engineered Salmonella typhimurium expressing TIMP-2 as a therapeutic intervention in an orthotopic glioma mouse model
- Source :
- Cancer Letters. 433:140-146
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Glioma is one of the most devastating and refractory cancers. The main factors underlying therapeutic failure include extremely invasive characteristics and lack of effective methods for drug delivery. Attenuated Salmonella strains presented a high concentration of tumor targets in various types of cancer models, suggesting a role as potential vectors for drug delivery. In this study, we genetically engineered an attenuated strain of Salmonella as an anti-invasive vector for the targeted delivery and expression of tissue inhibitor of metalloproteinases 2 (TIMP-2) in an orthotopic nude mouse model of glioma. The bioluminescence signals related to tumor size significantly declined in the TIMP-2-expressing Salmonella (SLpTIMP-2)-treated group compared with the control group. Compared with the control group with a survival rate of an average of 33 days, the SLpTIMP-2 group showed an extended survival rate by nearly 60% and lasted an average period of 53 days with TIMP-2 induction. These results indicated the promising therapeutic potential of S. typhimurium for targeted delivery and secretion of TIMP-2 in glioma.
- Subjects :
- Male
Salmonella typhimurium
0301 basic medicine
Cancer Research
Salmonella
Matrix metalloproteinase
Vaccines, Attenuated
medicine.disease_cause
Cancer Vaccines
Mice
03 medical and health sciences
Nude mouse
Cell Line, Tumor
Glioma
medicine
Animals
Humans
Vector (molecular biology)
Survival rate
Tissue Inhibitor of Metalloproteinase-2
biology
Brain Neoplasms
business.industry
Cancer
medicine.disease
biology.organism_classification
Xenograft Model Antitumor Assays
Guanine Nucleotides
030104 developmental biology
Oncology
Drug delivery
Cancer research
Matrix Metalloproteinase 2
Genetic Engineering
business
Subjects
Details
- ISSN :
- 03043835
- Volume :
- 433
- Database :
- OpenAIRE
- Journal :
- Cancer Letters
- Accession number :
- edsair.doi.dedup.....783db9fc85f8f9d1305016e90494300d
- Full Text :
- https://doi.org/10.1016/j.canlet.2018.06.031