AAV-mediated gene transfer of human pigment epithelium-derived factor inhibits Lewis lung carcinoma growth in mice.
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.
State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
Sha-Sha
SS
He
Hua-Shan
HS
Shi
Tao
T
Yin
Yong-Xia
YX
Li
Shun-Tao
ST
Luo
Qin-Jie
QJ
Wu
Lian
L
Lu
Yu-Quan
YQ
Wei
Li
L
Yang
D000818:Animals; D017209:Apoptosis; D002196:Capillaries / Q000473:pathology; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D000229:Dependovirus / Q000235:genetics* / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D005822:Genetic Vectors / Q000633:toxicity; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D009414:Nerve Growth Factors / Q000235:genetics* / Q000378:metabolism; D015843:Serpins / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor