Transduction of hepatocellular carcinoma (HCC) using recombinant adeno-associated virus (rAAV):: in vitro and in vivo effects of genotoxic agents
Transduction of hepatocellular carcinoma (HCC) using recombinant adeno-associated virus (rAAV):: in vitro and in vivo effects of genotoxic agents
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DOI：
10.1016/s0168-8278(00)80102-6
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发表时间：
2000-06-01
影响因子：
25.7
通讯作者：
Prieto, J
中科院分区：
文献类型：
--
作者：
Peng, DC;Qian, C;Prieto, J
背景/目的：腺相关病毒（AAV）是一种有吸引力的基因治疗工具。本文研究了腺相关病毒（AAV）载体对肝癌细胞（HCC）的体内、外转导作用，以及不同的转导策略对肿瘤细胞转导的影响（rAAV/ lacZ）表达。腺病毒辅助或用γ射线或拓扑异构酶抑制剂依托泊苷预处理HCC细胞导致体外细胞转导的显著增强，在具有皮下HCC肿瘤的裸鼠中的体内研究表明，HCC细胞不被单独的AAV载体转导。然而，肿瘤与腺病毒的共感染允许报告基因的有效表达，但仅在载体注射部位。先前用1800 rad的皮下肿瘤的γ-照射能够使用重组AAV改善HCC细胞的转导（高达30%）。在肝脏中具有HCC肿瘤的布法罗大鼠中连续i. p.输注依托泊苷导致正常肝组织和非常小的肿瘤病变的转导（
Background/Aims: Adeno-associated virus (AAV) is an attractive tool for gene therapy. Here we investigated the in vitro and in vivo transduction of hepatocellular carcinoma (HCC) cells by an AAV vector and the efficacy of different strategies to enhance the transduction of the tumor.Methods: Transduction efficiency was determined by analyzing AAV-mediated beta-galactosidase gene (rAAV/ lacZ) expression.Results: Adenovirus help or pretreatment of HCC cells with gamma-irradiation or with the topoisomerase inhibitor etoposide resulted in marked enhancement of cell transduction in vitro, In vivo studies in nude mice with subcutaneous HCC tumors showed that HCC cells were not transduced by AAV vector alone. However, co-infection of the tumor with adenovirus allowed an efficient expression of the reporter gene but only at the sites of vector injection. Previous gamma-irradiation of subcutaneous tumors with 1800 rad was able to improve transduction of HCC cells (up to 30%) using recombinant AAV Continuous i.p. infusion of etoposide in buffalo rats harboring HCC tumors in the liver resulted in transduction of normal liver tissue and also of very small neoplastic lesions (