title: Gene therapy with recombinant adenovirus encoding endostatin encapsulated in cationic liposome in coxsackievirus and adenovirus receptor-deficient colon carcinoma murine models.
abstract: Adenovirus (Ad)-based antiangiogenesis gene therapy is a promising approach for cancer treatment. Downregulation or loss of coxsackievirus and adenovirus receptor (CAR) is often detected in various human cancers, which hampers adenoviral gene therapy approaches. Cationic liposome-complexed adenoviral vectors have been proven useful in CAR-deficient cells to enhance therapeutic gene transfer in vivo. Here, we investigated the antitumor effects of recombinant adenovirus encoding endostatin (Ad-hE) encapsulated in cationic liposome (Ad-hE/Lipo) on CAR-deficient CT26 colon carcinoma murine models. In vitro, Ad-hE/Lipo enhanced adenovirus transfection in CAR-deficient cells (CT26), and endostatin gene expression was measured by both qualitative and quantitative detection. In addition, an antibody neutralizing assay indicated that neutralizing serum inhibited naked adenovirus 5 (Ad5) at rather higher dilution than the complexes of Ad5 and cationic liposomes (Ad5-CL), which demonstrated that Ad5-CL was more capable of protecting Ad5 from neutralization. In vivo, Ad-hE/Lipo treatment in the murine CT26 tumor model by intratumoral injection resulted in marked suppression of tumor growth and prolonged survival time, which was associated with a decreased number of microvessels and increased apoptosis of tumor cells. In conclusion, recombinant endostatin adenovirus encapsulated with cationic liposome effectively inhibited CAR-deficient tumor growth through an antiangiogenic mechanism in murine models without marked toxicity, thus showing a feasible strategy for clinical applications.
authors: State Key Lab of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
authors: Lian
authors: L
authors: Wang
authors: Bin
authors: B
authors: Yao
authors: Qiu
authors: Q
authors: Li
authors: Kai
authors: K
authors: Mei
authors: Jian-Rong
authors: JR
authors: Xu
authors: Hong-Xia
authors: HX
authors: Li
authors: Yong-Sheng
authors: YS
authors: Wang
authors: Yan-Jun
authors: YJ
authors: Wen
authors: Xiao-Dong
authors: XD
authors: Wang
authors: Han-Shuo
authors: HS
authors: Yang
authors: Yu-Hua
authors: YH
authors: Li
authors: Feng
authors: F
authors: Luo
authors: Yang
authors: Y
authors: Wu
authors: Yan-You
authors: YY
authors: Liu
authors: Li
authors: L
authors: Yang