Development of molecular target therapy using new angiogenin inhibitor against cancer induced bone diseases

破骨细胞介导的骨吸收在肿瘤的骨侵袭或骨破坏中起重要作用。本研究以血管生成因子血管生成素(Ang)为分子靶点，研究Ang抑制剂的治疗作用，并利用Ang-1基因敲除小鼠(Ang-KO)研究Ang的作用。与野生型小鼠(WT)相比，Ang-KO组生长早期的骨小梁形成受到抑制，Ang-KO细胞的体外破骨细胞形成受到抑制，但在体内模型中差异不大。血管紧张素转换酶抑制剂能够证实对小鼠癌症骨破坏模型的实用性。新药Terrein抑制血管生成，不仅具有抑制血管生成的作用，而且具有抗肿瘤活性。因此，建议使用血管紧张素转换酶抑制剂来治疗癌症所致的骨病。

Osteoclast-mediated bone resorption plays an important role in bone invasion or bone destruction of the cancer. We have been establishing the treatment of the cancer induced-bone diseases which assumed angiogenesis factor, angiogenin (ANG) as a molecular target.In the present study, we examined a therapeutic utility of ANG inhibitor and investigated the role of ANG using ANG-1 knockout mouse (ANG-KO). Trabecular bone formation of the early period of growth was suppressed in ANG-KO compare to the wild type mice (WT), and the in vitro osteoclasts formation using cells of ANG-KO was inhibited, but there were few differences in vivo model. The ANG inhibitor was able to confirm a utility for a mouse cancer bone destruction model. Newly developed medicine, Terrein, which inhibit the production of ANG, had not only the inhibition of angiogenesis, but also the antitumor activity. Therefore, a utility of ANG inhibitors against the cancer induced bone diseases was suggested.