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Adeno-associated virus-mediated doxycycline-regulatable TRAIL expression suppresses growth of human breast carcinoma in nude mice
- Source :
- BMC Cancer, BMC Cancer, Vol 12, Iss 1, p 153 (2012)
- Publication Year :
- 2011
-
Abstract
- Background Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) functions as a cytokine to selectively kill various cancer cells without toxicity to most normal cells. Numerous studies have demonstrated the potential use of recombinant soluble TRAIL as a cancer therapeutic agent. We have showed previous administration of a recombinant adeno-associated virus (rAAV) vector expressing soluble TRAIL results in an efficient suppression of human tumor growth in nude mice. In the present study, we introduced Tet-On gene expression system into the rAAV vector to control the soluble TRAIL expression and evaluate the efficiency of the system in cancer gene therapy. Methods Controllability of the Tet-On system was determined by luciferase activity assay, and Western blotting and enzyme-linked immunoabsorbent assay. Cell viability was determined by MTT assay. The breast cancer xenograft animal model was established and recombinant virus was administrated through tail vein injection to evaluate the tumoricidal activity. Results The expression of soluble TRAIL could be strictly controlled by the Tet-On system in both normal and cancer cells. Transduction of human cancer cell lines with rAAV-TRE-TRAIL&rAAV-Tet-On under the presence of inducer doxycycline resulted in a considerable cell death by apoptosis. Intravenous injection of the recombinant virus efficiently suppressed the growth of human breast carcinoma in nude mice when activated by doxycycline. Conclusion These data suggest that rAAV-mediated soluble TRAIL expression under the control of the Tet-On system is a promising strategy for breast cancer therapy.
- Subjects :
- Cancer Research
Programmed cell death
Genetic enhancement
viruses
Genetic Vectors
Gene Expression
Mice, Nude
Apoptosis
Breast Neoplasms
TRAIL
medicine.disease_cause
Recombinant virus
lcsh:RC254-282
Cell Line
TNF-Related Apoptosis-Inducing Ligand
Mice
Gene therapy
Adeno-associated virus
Cell Line, Tumor
Genetics
medicine
Animals
Humans
MTT assay
Viability assay
Controllable gene expression
Cell Proliferation
Tet-On
business.industry
Carcinoma
Genetic Therapy
Dependovirus
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Virology
Tumor Burden
Oncology
Doxycycline
Cancer cell
Cancer research
Female
business
Research Article
Subjects
Details
- ISSN :
- 14712407
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- BMC cancer
- Accession number :
- edsair.doi.dedup.....5f888f5c18fd4606a18eabaf1a53191b