Adeno-associated virus mediated endostatin gene therapy in combination with topoisomerase inhibitor effectively controls liver tumor in mouse model  

作　　者：SungYiHong MyunHeeLee WooJinHyung SungHoonNoh SeungHoChoi Kyung Sup Kim HyunCheolJung JaeKyungRoh 

机构地区：[1]Department of Surgery,Yonsei University College of Medicine,Seoul,Korea [2]Institute of Genetic Science,Department of Biochemistry and Molecular Biology,Yonsei University College of Medicine,Seoul,Korea [3]Oncology,Internal Medicine,Cancer Metastasis Research Center,Yonsei University College of Medicine

出　　处：《World Journal of Gastroenterology》2004年第8期1191-1197,共7页世界胃肠病学杂志（英文版）

基　　金：Supported by a faculty research grant of Yonsei University College of Medicine for 2002,No.2002-06

摘　　要：AIM:rAAV mediated endostatin gene therapy has been examined as a new method for treating cancer.However, a sustained and high protein delivery is required to achieve the desired therapeutic effects.We evaluated the impact of topoisomerase inhibitors in rAAV delivered endostatin gene therapy in a liver tumor model. METHODS:rAAV containing endostatin expression cassettes were transduced into hepatoma cell lines.To test whether the topoisomerase inhibitor pretreatment increased the expression of endostatin,Western blotting and ELISA were performed.The biologic activity of endostatin was confirmed by endothelial cell proliferation and tube formation assays. The anti-tumor effects of the rAAV-endostatin vector combined with a topoisomerase inhibitor,etoposide,were evaluated in a mouse liver tumor model. RESULTS:Topoisomerase inhibitors,including camptothecin and etoposide,were found to increase the endostatin exPression level in vitro.The over-expressed endostatin, as a result of pretreatment with a topoisomerase inhibitor, was also biologically active.In animal experiments,the combined therapy of topoisomerase inhibitor,etoposide with the rAAV-endostatin vector had the best tumor- suppressive effect and tumor foci were barely observed in livers of the treated mice.Pretreatment with an etoposide increased the level of endostatin in the liver and serum of rAAV-endostatin treated mice.Finally,the mice treated With rAAV-endostatin in combination with etoposide showed the longest survival among the experimental models. CONCLUSION:rAAV delivered endostatin gene therapy in combination with a topoisomerase inhibitor pretreatment is an effective modality for anticancer gene therapy.rAAV mediated endostatin gene therapy has beenexamined as a new method for treating cancer. However,a sustained and high protein delivery is required to achievethe desired therapeutic effects. We evaluated the impactof topoisomerase inhibitors in rAAV delivered endostatingene therapy in a liver tumor model.

关 键 词：ADENOVIRIDAE Animals Antineoplastic Agents Antineoplastic Agents  Phytogenic CAMPTOTHECIN Carcinoma  Hepatocellular Cell Line  Tumor Combined Modality Therapy DNA Topoisomerases inhibitors Drug Synergism ENDOSTATINS Endothelium  Vascular Enzyme Inhibitors ETOPOSIDE Gene Expression Gene Therapy Humans Liver Neoplasms Mice Research Support  Non-U.S. Gov't SARCOMA Survival Rate Umbilical Veins 

分 类 号：R735.7[医药卫生—肿瘤]