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The disintegrin echistatin in combination with doxorubicin targets high-metastatic human osteosarcoma overexpressing αvβ3 integrin in chick embryo and nude mouse models

机译:Disintegrin echistatin与阿霉素的结合可在鸡胚和裸鼠模型中靶向高转移性人骨肉瘤中过表达αvβ3整联蛋白

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摘要

Echistatin, a cyclic RGD peptide, which is an antagonist of αvβ3 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 αvβ3 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 αvβ3 integrin may be a target for osteosarcoma.
机译:Echistatin是一种环状RGD肽,是αvβ3整联蛋白(disintegrin)的拮抗剂,可抑制鸡绒毛膜绒毛膜(CAM)模型中的人骨肉瘤以及裸鼠原位裸鼠模型中的肿瘤生长和肺转移。使用了高表达αvβ3整联蛋白的人骨肉瘤高转移变体143B-LM4。 echistatin显着抑制CAM中高转移性143B-LM4细胞的肿瘤血管生成(P <0.05),与总体生长一样。与未经治疗的对照组(P <0.01)或单独的DOX(P <0.05)相比,阿霉素(DOX)-echistatin组合抑制裸鼠原位肿瘤的生长。用DOX-echistatin组合治疗的荷瘤小鼠比单独用DOX或对照PBS治疗的荷瘤小鼠存活时间更长(分别为P <0.01和P <0.01)。 Echistatin还抑制裸鼠中143B-LM4细胞的实验性肺转移。这些结果表明,DOX与整联蛋白联用具有治疗骨肉瘤的潜力,αvβ3整联蛋白可能是骨肉瘤的靶标。

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