Thrombin inhibitor, argatroban, prevents tumor cell migration and bone metastasis
Thrombin inhibitor, argatroban, prevents tumor cell migration and bone metastasis
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DOI：
10.1159/000081004
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发表时间：
2004-01-01
期刊：
影响因子：
3.5
通讯作者：
Uchida, A
中科院分区：
文献类型：
--
作者：
Asanuma, K;Wakabayashi, H;Uchida, A
众所周知，恶性肿瘤细胞具有促凝血活性，这与其转移潜能有关。凝血酶是凝血系统的关键酶，在肿瘤细胞周围产生，促进肿瘤细胞的迁移和转移。在本研究中，我们评价了特异性凝血酶抑制剂阿加曲班对B16BL6黑色素瘤细胞迁移和转移的影响。在体外，阿加曲班呈剂量依赖性地抑制细胞迁移，当阿加曲班存在时，最大的抑制被观察到(p<；0.0001)。为了研究凝血酶抑制剂的抗肿瘤作用，我们使用了我们之前报道过的动物模型。将B16黑色素瘤细胞移植到C57BL6小鼠的背侧皮下，将B16黑色素瘤细胞注入左心内。与安慰剂相比，腹膜内注射阿加曲班(每天9 mg/kg，连续4周)显著减少了转移灶的肢体数量(p<；0.05)。这些结果表明，阿加曲班通过抑制细胞迁移与减少黑色素瘤转移有关。结果表明，阿加曲班对骨转移瘤的治疗是有效的。版权所有(C)2004 S.Karger AG，巴塞尔。
It is well known that malignant cells show procoagulant activity, which is associated with their metastatic potential. Thrombin, the key enzyme of the blood coagulation system, is generated around tumor cells, promoting the migration and metastasis of tumor cells. In this study, we evaluated the effect of argatroban, a specific thrombin inhibitor, on the migration and metastasis of B16BL6 melanoma cells. In vitro argatroban dose-dependently inhibited cell migration, the maximum inhibition being observed in the presence of 10 muM argatroban (p < 0.0001). In order to investigate the antimetastatic effect of the thrombin inhibitor, we used an animal model that we have reported previously. C57BL6 mice which had received a bone (femur or tibia) transplanted into the dorsal subcutis were injected with B16 melanoma cells into the left heart ventricle. Intraperitoneal injection of argatroban (9 mg/kg/day for 4 weeks) significantly reduced the number of limbs with metastatic lesions as compared to a placebo (p < 0.05). These results suggest that argatroban was associated with reduced melanoma metastases by inhibiting cell migration. Our results showed that argatroban is effective for treatment of bone metastasis. Copyright (C) 2004 S. Karger AG, Basel.