Tome Yasunori, Kimura Hiroaki, Sugimoto Naotoshi, Tsuchiya Hiroyuki, Kanaya Fuminori, Bouvet Michael, Hoffman Robert M
AntiCancer, Inc., San Diego, CA 92111, USA.
Department of Surgery, University of California, San Diego, CA 92103, USA.
Oncotarget. 2016 Dec 27;7(52):87031-87036. doi: 10.18632/oncotarget.13497.
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.
水蛭素是一种环状RGD肽，是αvβ3整合素（去整合素）的拮抗剂，在鸡胚绒毛尿囊膜（CAM）模型中可抑制人骨肉瘤，在裸鼠原位模型中可抑制肿瘤生长和肺转移。使用了一种高转移性的人骨肉瘤变体143B-LM4，其αvβ3整合素过表达。水蛭素可显著抑制CAM中高转移性变体143B-LM4细胞的肿瘤血管生成（P<0.05）以及整体生长。与未治疗的对照组（P<0.01）或单独使用阿霉素（DOX）（P<0.05）相比，DOX-水蛭素联合用药可抑制裸鼠原位肿瘤生长。接受DOX-水蛭素联合治疗的荷瘤小鼠比单独接受DOX治疗或对照PBS治疗的小鼠存活时间更长（分别为P<0.01和P<0.01）。水蛭素还可抑制裸鼠中143B-LM4细胞的实验性肺转移。这些结果表明，DOX与去整合素联合使用有治疗骨肉瘤的潜力，且αvβ3整合素可能是骨肉瘤的一个靶点。
