AAV-mediated gene transfer of human pigment epithelium-derived factor inhibits Lewis lung carcinoma growth in mice.
AAV-mediated gene transfer of human pigment epithelium-derived factor inhibits Lewis lung carcinoma growth in mice.
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DOI：
10.3892/or.2012.1621
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发表时间：
2012-04
期刊：
影响因子：
4.2
通讯作者：
Yang L
中科院分区：
文献类型：
--
作者：
He SS;Shi HS;Yin T;Li YX;Luo ST;Wu QJ;Lu L;Wei YQ;Yang L
色素上皮衍生因子（PEDF）是哺乳动物眼血管生成最有效的抑制剂，最近已确定PEDF发挥其抗肿瘤活性的机制。本研究的目的是评价腺相关病毒（AAV）载体介导的人PEDF对刘易斯肺癌（LCC）细胞生长的抑制作用。瘤内注射AAV-PEDF导致肿瘤体积显著减小，并延长了携带LLC细胞的小鼠的存活时间，这与肿瘤中微血管密度降低和细胞凋亡增加有关。AAV载体代表了一种非常有前途的癌症基因治疗工具。通过监测动物体重以及基本器官结构和组织学形态的变化，并通过分析小鼠肝脏和肾脏功能，未检测到与AAV相关的明显毒性。我们的研究结果表明，AAV介导的PEDF基因表达可能提供一个积极的方法来抑制LLC的生长和治疗与AAV-PEDF可能提供一个有前途的治疗策略，在肺癌治疗。
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.
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