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Liposomes complexed to plasmids encoding angiostatin and endostatin inhibit breast cancer in nude mice
1Department of Pathology and Greenebaum Cancer Center, University of Maryland, Baltimore 21201, USA.
Abstract:
Gene therapy transfer of angiostatin and endostatin represents an alternative method of delivering angiogenic polypeptide inhibitors. We examined whether liposomes complexed to plasmids encoding angiostatin or endostatin inhibited angiogenesis and the growth of MDA-MB-435 tumors implanted in the mammary fat pads of nude mice. We determined that plasmids expressing angiostatin (PCI-Angio) or endostatin (PCI-Endo) effectively reduced angiogenesis using an in vivo Matrigel assay. We then investigated the efficacy of these plasmids in reducing the size of tumors implanted in the mammary fat pad of nude mice. Both PCI-Angio and PCI-Endo significantly reduced tumor size when injected intratumorally (P < 0.05). Compared to the untreated control group, the mice treated with PCI-Angio and PCI-Endo exhibited a reduction in tumor size of 36% and 49%, respectively. In addition, we found that i.v. injections of liposomes complexed to PCI-Endo reduced tumor growth in the nude mice by nearly 40% when compared to either empty vector (PCI) or untreated controls (P < 0.05). These findings provide a basis for the further development of nonviral delivery of antiangiogenic genes.
Insights
Gene therapy using plasmids encoding angiostatin or endostatin effectively inhibited tumor growth and angiogenesis in mice. Nonviral liposome delivery of these anti-angiogenic genes shows promise for cancer treatment development.
Area of Science:
- Molecular Biology
- Cancer Research
- Gene Therapy
Background:
- Angiogenesis is crucial for tumor growth.
- Angiostatin and endostatin are potent inhibitors of angiogenesis.
- Gene therapy offers a novel approach for delivering anti-angiogenic factors.
Purpose of the Study:
- To evaluate the efficacy of gene therapy using plasmids encoding angiostatin or endostatin.
- To assess the inhibition of angiogenesis and tumor growth in a mouse model.
- To investigate nonviral liposome-based delivery of anti-angiogenic genes.
Main Methods:
- In vivo Matrigel assay to assess angiogenesis.
- Intratumoral and intravenous injection of plasmids complexed with liposomes into nude mice bearing MDA-MB-435 tumors.
- Measurement of tumor size reduction and comparison with control groups.
Main Results:
- Plasmids expressing angiostatin (PCI-Angio) and endostatin (PCI-Endo) significantly reduced angiogenesis.
- Intratumoral injection of PCI-Angio and PCI-Endo reduced tumor size by 36% and 49%, respectively.
- Intravenous injection of liposomes with PCI-Endo decreased tumor growth by nearly 40%.
Conclusions:
- Gene therapy with angiostatin and endostatin is effective in inhibiting tumor growth and angiogenesis.
- Liposome-mediated nonviral delivery of anti-angiogenic genes is a viable strategy.
- These findings support further development of gene therapy for cancer treatment.