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Endostatin gene therapy on murine lung metastases model utilizing cationic vector-mediated intravenous gene delivery
Y Nakashima1, M Yano, Y Kobayashi
1Department of Surgery II, Nagoya City University Medical School, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Abstract:
Tumors require ongoing angiogenesis to support their growth. Inhibition of angiogenesis by production of antiangiogenic factors should be a viable approach for cancer gene therapy. In this study, we investigated whether intravenous administration of endostatin gene complexed with a cationic vector (GL67/DOPE or PEI22K) could inhibit the development of lung tumors in mice injected i.v. with NFSa Y83 fibrosarcoma cells (5 x 10(5)) which frequently form lung metastasis. mRNA and protein of the transfected gene were produced in the lung and other organs of the transfected mice as assessed by immunohistochemistry, Western blotting and reverse transcription-polymerase chain reaction. Single intravenous injection of the endostatin gene (60 microg) complexed with either GL67/DOPE or PEI22K on day 3 or day 7 after fibrosarcoma cell inoculation significantly inhibited tumor formation in the lung as evidenced by the reduced number of lung tumors and lung weight, and prolonged survival of the endostatin gene-transfected mice compared with control mice. These findings suggested that the endostatin gene therapy, using cationic vector-mediated intravenous gene transfer, might be a feasible strategy for organ-targeted prevention and regulation of possible disseminated cancers.
Insights
Intravenous endostatin gene therapy effectively inhibited lung tumor development in mice. This cancer gene therapy approach, using cationic vectors, offers a potential strategy for preventing disseminated cancers.
Area of Science:
- Oncology
- Gene Therapy
- Molecular Biology
Background:
- Tumor growth necessitates continuous angiogenesis.
- Inhibiting angiogenesis via antiangiogenic factors is a promising cancer gene therapy strategy.
Purpose of the Study:
- To investigate the efficacy of intravenous endostatin gene therapy in preventing lung tumor development.
- To assess the potential of cationic vectors (GL67/DOPE, PEI22K) for endostatin gene delivery.
Main Methods:
- Mice were intravenously injected with NFSa Y83 fibrosarcoma cells and subsequently received endostatin gene complexed with cationic vectors.
- Gene expression (mRNA and protein) was confirmed in lung and other organs using immunohistochemistry, Western blotting, and RT-PCR.
- Tumor formation, lung weight, and survival rates were evaluated in treated and control groups.
Main Results:
- Significant inhibition of lung tumor formation was observed following endostatin gene therapy.
- Reduced lung tumor number and lung weight were noted in treated mice.
- Endostatin gene therapy prolonged the survival of mice with lung tumors.
Conclusions:
- Intravenous endostatin gene therapy using cationic vectors is a feasible strategy for preventing lung tumors.
- This approach holds potential for organ-targeted prevention and management of disseminated cancers.