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

Authors
 Sung Yi Hong  ;  Myun Hee Lee  ;  Seung Ho Choi  ;  Sung Hoon Noh  ;  Woo Jin Hyung  ;  Jae Kyung Roh  ;  Hyun Cheol Jung  ;  Kyung Sup Kim 
Citation
 WORLD JOURNAL OF GASTROENTEROLOGY, Vol.10(8) : 1191-1197, 2004 
Journal Title
 WORLD JOURNAL OF GASTROENTEROLOGY 
ISSN
 1007-9327 
Issue Date
2004
MeSH
Adenoviridae/genetics* ; Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents, Phytogenic/pharmacology ; Camptothecin/pharmacology* ; Carcinoma, Hepatocellular/drug therapy* ; Carcinoma, Hepatocellular/mortality ; Cell Line, Tumor ; Combined Modality Therapy ; Drug Synergism ; Endostatins/pharmacology ; Endothelium, Vascular/cytology ; Enzyme Inhibitors/pharmacology* ; Etoposide/pharmacology ; Gene Expression/drug effects ; Genetic Therapy/methods* ; Humans ; Liver Neoplasms/drug therapy* ; Liver Neoplasms/mortality ; Mice ; Sarcoma/drug therapy* ; Sarcoma/mortality ; Survival Rate ; Topoisomerase Inhibitors ; Umbilical Veins/cytology
Abstract
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.
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Sup(김경섭) ORCID logo https://orcid.org/0000-0001-8483-8537
Noh, Sung Hoon(노성훈) ORCID logo https://orcid.org/0000-0003-4386-6886
Roh, Jae Kyung(노재경)
Lee, Myun Hee(이면희)
Chung, Hyun Cheol(정현철) ORCID logo https://orcid.org/0000-0002-0920-9471
Choi, Seung Ho(최승호) ORCID logo https://orcid.org/0000-0002-9872-3594
Hyung, Woo Jin(형우진) ORCID logo https://orcid.org/0000-0002-8593-9214
Hong, Sung Yi(홍성이)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/113102
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