Recombinant adeno-associated virus 2-mediated antiangiogenic prevention in a mouse model of intraperitoneal ovarian cancer
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Updated: Aug 19, 2026
An Orthotopic Model of Serous Ovarian Cancer in Immunocompetent Mice for in vivo Tumor Imaging and Monitoring of Tumor Immune Responses
Published on: November 28, 2010
Tatyana Isayeva1, Changchun Ren, Selvarangan Ponnazhagan
1Department of Pathology, University of Alabama at Birmingham, 19th Street South, Birmingham, AL 35294-0007, USA.
Purpose:
In the present study, we sought to determine the potential of sustained transgene expression by a single i.m. administration of recombinant adeno-associated virus 2 (rAAV) encoding angiostatin and endostatin in inhibiting i.p. ovarian cancer growth and dissemination in a preclinical mouse model.
Experimental Design:
Cohorts of female athymic nude mice received either no virus or 1.2 x 10(11) particles of rAAV encoding green fluorescence protein or endostatin plus angiostatin, i.m. Three weeks later, the mice were i.p. injected with 10(6) human epithelial ovarian cancer cell line SKOV3.ip1. As a measure of effectiveness of the therapy, tumor weight, abdominal distension, ascites volume and vascular endothelial growth factor level, and tumor weight were determined. Immunohistochemistry was done to determine tumor cell apoptosis and endothelial cell proliferation following the therapy. Tumor-free survival was recorded as the end point.
Results:
Results indicated a significant tumor-free survival (P < 0.003) following therapy with rAAV encoding endostatin and angiostatin compared with untreated or rAAV-green fluorescence protein-treated mice. Ascites volume in rAAV endostatin and angiostatin-treated mice was significantly lower than naive mice and contained less hemorrhage and tumor conglomerates. The level of vascular endothelial growth factor in the ascites of antiangiogenic vector treated mice was also significantly less compared with the untreated mice. Immunohistochemical analyses indicated increased tumor cell apoptosis and decreased blood vasculature following rAAV endostatin and angiostatin treatment.
Conclusion:
The results indicate that antiangiogenic genetic prevention from stable systemic levels of angiostatin and endostatin by i.m. administration of rAAV can be used for the treatment of i.p. ovarian cancer growth and dissemination.
Insights
Gene therapy using recombinant adeno-associated virus (rAAV) encoding angiostatin and endostatin significantly improved tumor-free survival in a preclinical ovarian cancer model. This approach offers a promising strategy for treating ovarian cancer growth and spread.
Area of Science:
- Oncology
- Gene Therapy
- Ovarian Cancer Research
Background:
- Ovarian cancer is a leading cause of cancer-related deaths in women.
- Current treatments often face challenges with resistance and recurrence.
- Targeting tumor angiogenesis is a key strategy in cancer therapy.
Purpose of the Study:
- To evaluate the efficacy of sustained transgene expression of angiostatin and endostatin via recombinant adeno-associated virus 2 (rAAV) delivery.
- To assess the inhibition of intraperitoneal (i.p.) ovarian cancer growth and dissemination in a preclinical mouse model.
Main Methods:
- Athymic nude mice received i.m. administration of rAAV encoding either green fluorescence protein (control) or endostatin and angiostatin.
- Mice were subsequently injected with human epithelial ovarian cancer cells (SKOV3.ip1).
- Tumor weight, ascites volume, vascular endothelial growth factor (VEGF) levels, apoptosis, and proliferation were analyzed. Tumor-free survival was the primary endpoint.
Main Results:
- Significant improvement in tumor-free survival was observed in mice treated with rAAV encoding endostatin and angiostatin (P < 0.003).
- Reduced ascites volume, less hemorrhage, and fewer tumor conglomerates were noted in the treated group.
- Decreased VEGF levels, increased tumor cell apoptosis, and reduced tumor vasculature were confirmed via immunohistochemistry.
Conclusions:
- Single i.m. administration of rAAV encoding angiostatin and endostatin leads to sustained transgene expression.
- This anti-angiogenic gene therapy effectively inhibits i.p. ovarian cancer growth and dissemination.
- rAAV-mediated delivery of anti-angiogenic factors presents a viable therapeutic strategy for ovarian cancer.
