首页|期刊导航|中华医学杂志（英文版）|Synergistic antitumor effects of in vivo production of human endostatin and tissue inhibitor of metalloproteinase-1 in mice after subcutaneous implantation of primary fibroblasts transfected by adenovirus-mediated gene delivery
Synergistic antitumor effects of in vivo production of human endostatin and tissue inhibitor of metalloproteinase-1 in mice after subcutaneous implantation of primary fibroblasts transfected by adenovirus-mediated gene delivery
SHEN Wei-gan ZHU Jun ZHANG Yu SU Qing
中华医学杂志（英文版）2010，Vol.123Issue(7)：922-928,7.
中华医学杂志（英文版）2010，Vol.123Issue(7)：922-928,7.DOI:10.3760/cma.j.issn.0366-6999.2010.07.029
Synergistic antitumor effects of in vivo production of human endostatin and tissue inhibitor of metalloproteinase-1 in mice after subcutaneous implantation of primary fibroblasts transfected by adenovirus-mediated gene delivery
Synergistic antitumor effects of in vivo production of human endostatin and tissue inhibitor of metalloproteinase-1 in mice after subcutaneous implantation of primary fibroblasts transfected by adenovirus-mediated gene delivery
摘要
Abstract
Background Tissue inhibitor of metalloproteinase (TIMP)-1 is a multifunctional protein. The aim of the study was to examine the feasibility of using a combination of adenovirus-mediated gene delivery of TIMP-1 plus endostatin and cell transplantation techniques to treat tumor growth and metastasis in mouse melanoma.Methods A enzyme-linked immunosorbent assay (ELISA) was used to detect the level of TIMP-1 and endostatin in vitro and in vivo. A tumor bearing mouse model and an experimental lung metastasis model in animal experiments were used to explore the therapeutic effect of in vivo production of human TIMP-1 and endostatin after the implantation of primary fibroblasts infected with the indicated adenovirus into tumor-bearing mice and a cytochemical method was used to observe histopathological changes of the tumor. An experimental lung metastasis model was established by injecting B16BL6 cells into the tail vein of mice and adenovirus-infected primary fibroblasts were subcutaneously implanted into the mice 24 hours later. Twenty-one days after tumor cell injection, mice were sacrificed to examine the effect on nodules visible as black forms on the surface of the lungs in B16BL6 cells.Results TIMP-1 and endostatin were secreted into the supernatants of cultures of Ad-TIMP-1 and Ad-End-infected mouse primary fibroblasts. We also observed that implantation of fibroblasts infected with Ad-TIMP-1 alone, Ad-End alone, or Ad-TIMP-1 plus Ad-End resulted in detectable blood levels which may clearly inhibit the tumor growth and metastasis in a murine melanoma model.Conclusion These results suggest the high capacity of transfection for the delivery of TIMP-1 or endostatin gene constructs into primary fibroblasts, and demonstrate that the implantation of TIMP-1 and endostatin producing fibroblasts at a site in vivo where direct secretion of TIMP-1 and endostatin into the blood is possible represented a promising approach for the development of cancer therapy.关键词
tissue inhibitor of metalloproteinase-1/endostatin/melanoma/metastasis/primary fibroblastsKey words
tissue inhibitor of metalloproteinase-1/endostatin/melanoma/metastasis/primary fibroblasts引用本文复制引用
SHEN Wei-gan,ZHU Jun,ZHANG Yu,SU Qing..Synergistic antitumor effects of in vivo production of human endostatin and tissue inhibitor of metalloproteinase-1 in mice after subcutaneous implantation of primary fibroblasts transfected by adenovirus-mediated gene delivery[J].中华医学杂志（英文版）,2010,123(7):922-928,7.基金项目
This work was supported in part by grants from the Project of Priming Funding for PHD and the Fund Projects to Cultivate Scientific and Technological Innovation of Yangzhou University (China) (No. 2008CXJ048). （China）
