AAV-mediated gene transfer of human pigment epithelium-derived factor inhibits Lewis lung carcinoma growth in mice.

Abstract

Pigment epithelium-derived factor (PEDF) is the most potent inhibitor of angiogenesis in the mammalian eye, and mechanisms through which PEDF exerts its antitumour activity have recently been defined. The aim of our research was to evaluate the ability of adeno-associated virus (AAV) vector-mediated transfer of human PEDF to inhibit lewis lung carcinoma (LCC) cell growth. Intratumoural injection of AAV-PEDF caused significant reduction of the tumour volume and prolonged the survival time of mice bearing LLC cells, which were associated with decreased microvessel density and increased apoptosis in the tumours. AAV vectors represent a very promising tool for cancer gene therapy. No noticeable toxicity concerning AAV was detected as inferred from monitoring changes in animal body weight as well as basic organ structure and histological morphology, and by analyzing mouse liver and kidney function. Our findings indicate that AAV-mediated PEDF gene expression may offer an active approach to inhibit LLC growth and that treatment with AAV-PEDF may provide a promising therapeutic strategy in lung cancer treatment.

• Authors: Sha-Sha He, Hua-Shan Shi, Tao Yin, Yong-Xia Li, Shun-Tao Luo, Qin-Jie Wu, Lian Lu, Yu-Quan Wei, Li Yang
• Journal: Oncology reports (Oncol Rep) Vol. 27 Issue 4 Pg. 1142-8 (Apr 2012) ISSN: 1791-2431 [Electronic] Greece
• PMID: 22218393 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Eye Proteins
• Nerve Growth Factors
• Serpins
• pigment epithelium-derived factor

Topics

• Animals
• Apoptosis
• Capillaries (pathology)
• Carcinoma, Lewis Lung (blood supply, genetics, metabolism, pathology, therapy)
• Cell Line, Tumor
• Dependovirus (genetics, metabolism)
• Eye Proteins (genetics, metabolism)
• Genetic Therapy (adverse effects, methods)
• Genetic Vectors (toxicity)
• Human Umbilical Vein Endothelial Cells (metabolism)
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Neovascularization, Pathologic (genetics, metabolism, prevention & control)
• Nerve Growth Factors (genetics, metabolism)
• Serpins (genetics, metabolism)
• Time Factors
• Transfection
• Tumor Burden