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Title :The disintegrin echistatin in combination with doxorubicin targets high-metastatic human osteosarcoma overexpressing α_νβ_3 integrin in chick embryo and nude mouse models
Authors :Tome, Yasunori
Kimura, Hiroaki
Sugimoto, Naotoshi
Tsuchiya, Hiroyuki
Kanaya, Fuminori
Bouvet, Michael
Hoffman, Robert M.
Issue Date :22-Nov-2016
Abstract :Echistatin, a cyclic RGD peptide, which is an antagonist of α_vβ_3 integrin (disintegrin), inhibited human osteosarcoma in the chick chorioallontoic membrane (CAM) model and tumor growth and pulmonary metastases in a nude mouse orthotopic model. A high-metastatic variant of human osteosarcoma, 143B-LM4, overexpressing α_vβ_3 integrin was used. Tumor angiogenesis by high-metastatic variant 143B-LM4 cells in the CAM was significantly inhibited by echistatin (P<0.05) as was overall growth. A doxorubicin (DOX)-echistatin combination inhibited orthotopic tumor growth compared to untreated control (P<0.01) or DOX alone (P<0.05) in nude mice. Tumor-bearing mice treated with the DOX-echistatin combination survived longer than those treated with DOX alone or control PBS (P<0.01 and P<0.01, respectively). Echistatin also inhibited experimental lung metastasis of 143B-LM4 cells in nude mice. These results suggest that DOX in combination with a disintegrin has potential to treat osteosarcoma and that α_vβ_3 integrin may be a target for osteosarcoma.
URL :https://doi.org/10.18632/oncotarget.13497
Type Local :雑誌掲載論文
ISSN :1949-2553
Publisher :Impact Journals
URI :http://hdl.handle.net/20.500.12000/47547
Citation :Oncotarget Vol.7 no.52 p.87031 -87036
Appears in Collections:Peer-reviewed Journal Articles (Faculty of Medicine)

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