Angiogenesis Inhibitor Z24 Induces Endothelial Cell Apoptosis and Suppresses Tumor Growth and Metastasis

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概要

• 論文の詳細を見る

• Z24, a small molecular compound with similar chemical structure to SU5416 designed and synthesized by our lab, has been proved to be an angiogenesis inhibitor. In this study, Z24 was shown to induce human umbilical venous endothelial cell (HUVEC) apoptosis confirmed by morphologic changes including the presence of apoptotic bodies, significant apoptotic sub-G1 peak upon flow-cytometric analysis, formation of DNA ladders upon agarose gel electrophoresis, and TUNEL (TdT mediated X-dUTP nick-end labeling) results. Systemic administration of Z24 at non-toxic dose in nude mice resulted in inhibition of subcutaneous tumor growth of human colon cancer HCT-8, while it did not inhibit this cell line in vitro, with 100-fold more potent growth-inhibition against endothelial cells. The immunohistochemical results showed that the microvessel density of tumor tissue of the Z24 group was significantly lower than that of the control groups (P<0.05), which supported its anti-angiogenic property. We further found that Z24 inhibited the pulmonary metastasis of mouse lung adenocarcinoma LA795, with fewer surface lung metastases (89.6%, P<0.0001) and decreased lung weights (38.5%, P<0.01) compared to the vehicle group. All these findings support that Z24 is a promising angiogenesis inhibitor for limiting tumor growth and metastasis.

• 社団法人 日本薬理学会の論文
• 2005-04-20

著者

• Li Song

  Beijing Institute Of Pharmacology And Toxicology

• Wu Min

  National Laboratory Of Molecular Oncology Cancer Institute Chinese Academy Of Medical Sciences Pekin

• Lu Haiyan

  National Laboratory Of Molecular Oncology Cancer Institute Chinese Academy Of Medical Sciences Pekin

• Liang Xiao

  National Laboratory Of Molecular Oncology Cancer Institute Chinese Academy Of Medical Sciences Pekin

• Zheng Zhibing

  Beijing Institute Of Pharmacology And Toxicology

• LIN Chen

  National Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences, Pe

• GUO Shunxing

  Institute of Medical Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical Co

• ZHANG Xueyan

  National Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences, Pe

• FU Ming

  National Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences, Pe

• Zhang Xueyan

  National Laboratory Of Molecular Oncology Cancer Institute Chinese Academy Of Medical Sciences Pekin

• Guo Shunxing

  Institute Of Medical Plant Development Chinese Academy Of Medical Sciences Peking Union Medical Coll

• Fu Ming

  National Laboratory Of Molecular Oncology Cancer Institute Chinese Academy Of Medical Sciences Pekin

• Lin Chen

  National Laboratory Of Molecular Oncology Cancer Institute Chinese Academy Of Medical Sciences Pekin

• Zhang Xueyan

  National Institute Of Occupational Health And Poison Control Chinese Center For Disease Control And

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