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Potent anti-tumor effects of a dual specific oncolytic adenovirus expressing apoptin in vitro and in vivo
- Source :
- Molecular Cancer, Vol 9, Iss 1, p 10 (2010), Molecular Cancer
- Publication Year :
- 2010
- Publisher :
- BMC, 2010.
-
Abstract
- Background Oncolytic virotherapy is an attractive drug platform of cancer gene therapy, but efficacy and specificity are important prerequisites for success of such strategies. Previous studies determined that Apoptin is a p53 independent, bcl-2 insensitive apoptotic protein with the ability to specifically induce apoptosis in tumor cells. Here, we generated a conditional replication-competent adenovirus (CRCA), designated Ad-hTERT-E1a-Apoptin, and investigated the effectiveness of the CRCA a gene therapy agent for further clinical trials. Results The observation that infection with Ad-hTERT-E1a-Apoptin significantly inhibited growth of the melanoma cells, protecting normal human epidermal melanocytes from growth inhibition confirmed cancer cell selective adenoviral replication, growth inhibition, and apoptosis induction of this therapeutic approach. The in vivo assays performed by using C57BL/6 mice containing established primary or metastatic tumors expanded the in vitro studies. When treated with Ad-hTERT-E1a-Apoptin, the subcutaneous primary tumor volume reduction was not only observed in intratumoral injection group but in systemic delivery mice. In the lung metastasis model, Ad-hTERT-E1a-Apoptin effectively suppressed pulmonary metastatic lesions. Furthermore, treatment of primary and metastatic models with Ad-hTERT-E1a-Apoptin increased mice survival. Conclusions These data further reinforce the previously research showing that an adenovirus expressing Apoptin is more effective and advocate the potential applications of Ad-hTERT-E1a-Apoptin in the treatment of neoplastic diseases in future clinical trials.
- Subjects :
- Oncolytic adenovirus
Cancer Research
Lung Neoplasms
DNA, Recombinant
Gene Expression
Antineoplastic Agents
Apoptosis
Biology
medicine.disease_cause
lcsh:RC254-282
Adenoviridae
Mice
chemistry.chemical_compound
Subcutaneous Tissue
In vivo
Cell Line, Tumor
medicine
Animals
Humans
Transgenes
Melanoma
Telomerase
Cell Proliferation
Oncolytic Virotherapy
Research
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Survival Analysis
Primary tumor
Oncolytic virus
chemistry
Oncology
Organ Specificity
Cancer cell
Cancer research
Molecular Medicine
Adenovirus E1A Proteins
Growth inhibition
Apoptosis Regulatory Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 14764598
- Volume :
- 9
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Molecular Cancer
- Accession number :
- edsair.doi.dedup.....ed45c9f721cb213570657b21d803bc9d