Angiotensin II type1 receptor blocker(ARB) Inhibits colon cancer cell proliferation

血管紧张素 II 1 型受体阻滞剂 (ARB) 抑制结肠癌细胞增殖

• 批准号: 23790802
• 负责人: MIZUSHIMA Takashi
• 金额: $ 2.75万
• 依托单位: Nagoya City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23790802/
• 关键词: IBD; colitic cancer; AT1R; ARB; telmisarn; telmisartan; NF-κB

It is known that a disintegrin and metalloproteinase (ADAM) cleaves pro-heparin-binding epidermal growth factor-like growth factor (proHB-EGF), and the soluble HB-EGF activates EGFR. Simultaneously, the C-terminal fragment of proHB-EGF (HB-EGF-CTF) translocates into the inner nuclear membrane, and subsequently influences cell proliferation by binding nuclear promyelocytic leukemia zinc finger (PLZF) protein, a transcriptional repressor, which induces its nuclear export.We found that colon cancer cell proliferation is regulated via the nuclear translocation of HB-EGF C-terminal fragments. And we also found that telmisartan and its derivatives with biphenyl tetrazole completely blocked this association. We propose that the inhibition of HB-EGF-CTF nuclear translocation with telmisartan and its derivatives may lead to novel strategies that prevent cell proliferation in the development of colon cancer.

已知去整合素和金属蛋白酶（ADAM）切割前肝素结合表皮生长因子样生长因子（proHB-EGF），并且可溶性HB-EGF激活EGFR。同时，proHB-EGF的C端片段（HB-EGF-CTF）转位到细胞内膜，通过与转录抑制因子核早幼粒细胞白血病锌指蛋白（PLZF）结合，诱导其向细胞核输出，从而影响细胞增殖。我们还发现替米沙坦及其联苯四唑衍生物完全阻断了这种结合。我们认为，用替米沙坦及其衍生物抑制HB-EGF-CTF核转位可能会导致新的策略，防止结肠癌发展中的细胞增殖。

项目成果

大腸癌増殖シグナルHB-EGF-C 末端核移行をターゲットとした新規薬剤探索

寻找靶向结直肠癌生长信号HB-EGF-C末端核转位的新药

• 发表时间: 2012
• 作者: 野﨑昭人;木田沙緒里;田中春華;廣瀬春香;米澤広美;宮島栄治;木田沙緒里，野崎昭人，田中克明，田中春華，竹森美紀，廣瀬春香，米澤広美，宮島栄治;野崎昭人，近藤正晃，福田浩之，森本学，沼田和司，田中克明;尾関 啓司
• 通讯作者: 尾関 啓司