A novel angiogenesis inhibitor, Ki23057, is useful for preventing the progression of colon cancer and the spreading of cancer cells to the liver.
A novel angiogenesis inhibitor, Ki23057, is useful for preventing the progression of colon cancer and the spreading of cancer cells to the liver.
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DOI：
10.1016/j.ejca.2007.09.002
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发表时间：
2007-11
影响因子：
8.4
通讯作者：
Katsunobu Sakurai;N. Yamada;M. Yashiro;T. Matsuzaki;M. Komatsu;M. Ohira;A. Miwa;K. Hirakawa
中科院分区：
文献类型：
--
作者：
Katsunobu Sakurai;N. Yamada;M. Yashiro;T. Matsuzaki;M. Komatsu;M. Ohira;A. Miwa;K. Hirakawa
Ki 23057是一种新型的小分子合成酪氨酸激酶抑制剂，可阻断VEGF受体2（VEGFR 2）的自磷酸化。为了确定Ki 23057作为抗血管生成剂的作用，我们研究了Ki 23057在体外和体内对结肠癌和血管内皮细胞的作用。Ki 23057可抑制VEGF诱导的人脐静脉内皮细胞（HUVECs）增殖，但对3种结肠癌细胞（LM-H3、LoVo和LS 174 T）的增殖无抑制作用。Ki 23057抑制HUVECs管形成。免疫沉淀结果显示Ki 23057可抑制HUVECs中VEGFR 2的酪氨酸磷酸化。Ki 23057对异种移植的LM-H3肿瘤的生长和癌细胞向肝脏的扩散表现出显著的抑制作用。与对照相比，抗CD 31抗体在用Ki 23057处理的异种移植肿瘤中染色显著较少的微血管。Ki 23057有可能成为一种新的抗结肠癌血管生成药物。
Ki23057 is a new, small synthetic tyrosine kinase inhibitor that blocks autophosphorylation of the VEGF receptor2 (VEGFR2). To determine the effect of Ki23057 as an anti-angiogenic agent, we studied the effect of Ki23057 for colon cancer and vascular endothelial cells in vitro and in vivo. Ki23057 inhibited VEGF-induced proliferation of human umbilical vein endothelial cells (HUVECs), whereas no inhibitory effect of Ki23057 on the proliferation of three colon cancer cells (LM-H3, LoVo and LS174T) was observed by means of the cell count assay. Ki23057 inhibited tube formation of HUVECs. Immunoprecipitation demonstrated that Ki23057 inhibited tyrosine phosphorylation of VEGFR2 in HUVECs. Ki23057 exhibited a significant inhibitory effect on the growth of the xenografted LM-H3 tumours and the spreading of cancer cells to the liver. Anti-CD31 antibody stained significantly fewer microvessels in the xenografted tumours treated with Ki23057 compared with controls. Ki23057 may be a promising new antiangiogenic agent for colon cancer.