Tumor-targeted delivery of biologically active TRAIL protein
| Autor: | X. M. Zhang, J. H. Man, B. F. Jin, Jing Zhao, K. He, Peijing Zhang, H. Y. Li, Hui Zhang, W. L. Gong, Xin Pan, B. Liang, Chenhui Wang, Tao Li, W. H. Li, A. L. Li, T. Zhou |
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| Rok vydání: | 2010 |
| Předmět: |
Cancer Research
Blotting Western Genetic Vectors Mice Nude TRAIL Biology medicine.disease_cause Polymerase Chain Reaction Flow cytometry TNF-Related Apoptosis-Inducing Ligand Mice Cell Line Tumor Neoplasms medicine Escherichia coli Animals Humans Molecular Biology Mice Inbred BALB C medicine.diagnostic_test tumor targeting apoptosis Biological activity Genetic Therapy Original Articles Flow Cytometry Molecular biology Immunohistochemistry Blot Survival Rate Cell culture Apoptosis Toxicity Cancer research Molecular Medicine Tumor necrosis factor alpha Female |
| Zdroj: | Cancer Gene Therapy |
| ISSN: | 1476-5500 |
| Popis: | The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a potent inducer of tumor cell apoptosis, but concerns of considerable liver toxicity limit its uses in human cancer therapy. Here, we show that i.v. injected Escherichia coli DH5alpha (E. coli DH5alpha) specifically replicates in solid tumors and metastases in live animals. E. coli DH5alpha does not enter tumor cells and suits for being the vector for soluble TRAIL (sTRAIL), which induces apoptosis by activating cell-surface death receptors. With the high 'tumor-targeting' nature, we demonstrate that intratumoral (i.t.) and intravenous injection of sTRAIL-expressing E. coli DH5alpha results in the tumor-targeted release of biologically active molecules, which leads to a dramatic reduction in the tumor growth rate and the prolonged survival of tumor-bearing mice. TRAIL delivery by E. coli DH5alpha did not cause any detectable toxicity to any organs, suggesting that E. coli DH5alpha-delivered sTRAIL protein therapy may provide a feasible and effective form of treatment for solid tumors. |
| Databáze: | OpenAIRE |
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