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

已知去整合素和金属蛋白酶(ADAM)裂解前肝素结合的表皮生长因子样生长因子(proHB-EGF)，而可溶性HB-EGF激活EGFR。同时，ProHB-EGF(HB-EGF-CTF)的C末端片段移位到核内核膜，通过结合转录抑制因子锌指蛋白(PLZF)而影响细胞增殖，从而诱导其核输出。我们还发现替米沙坦及其衍生物与联苯四唑完全阻断了这种联系。我们认为，替米沙坦及其衍生物抑制HB-EGF-CTF核转位可能导致在结肠癌发生过程中防止细胞增殖的新策略。

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.