Angiotensin II augmented migration and invasion of choriocarcinoma cells involves PI3K activation through the AT1 receptor
Angiotensin II augmented migration and invasion of choriocarcinoma cells involves PI3K activation through the AT1 receptor
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DOI：
10.1016/j.placenta.2005.07.001
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发表时间：
2006-06-01
期刊：
影响因子：
3.8
通讯作者：
Kikkawa, F.
中科院分区：
文献类型：
--
作者：
Ishimatsu, S.;Itakura, A.;Kikkawa, F.
血管紧张素II(Ang II)通过激活纤溶酶原激活物抑制物-1(PAI-1)抑制绒毛外滋养层细胞的迁移，但目前尚不清楚它是刺激还是抑制绒毛癌细胞的恶性行为。由于我们先前发现肾素-血管紧张素系统(RAS)通过血管紧张素Ⅱ1型受体(AT1R)调节绒毛癌细胞(BeWo)的增殖能力，因此，在本研究中，我们利用Transwell细胞培养箱研究了Ang II对绒毛癌细胞体外迁移/侵袭的影响。棋盘分析显示，Ang II(10(-8)M)可促进绒毛膜癌细胞系的迁移和侵袭，并增加细胞的随机迁移率。免疫印迹显示Ang II可激活BeWo细胞FAK和Akt的磷酸化。此外，血管紧张素Ⅱ对细胞迁移的影响可被选择性AT1R拮抗剂和磷脂酰肌醇3-激酶(PI3K)抑制剂所消除。提示血管紧张素转换酶II诱导的绒毛膜癌细胞迁移和侵袭可能与AT1R结合后的PI3K有关。
While angiotensin II (Ang II) has been shown to inhibit migration of extravillous trophoblasts via plasminogen activator inhibitor-1 (PAI-1) activation, it has remained unclear whether it stimulates or inhibits malignant behavior of choriocarcinoma cells. Since we previously found an involvement of the renin-angiotensin system (RAS) in the proliferative potential in choriocarcinoma cells (BeWo), mediated via the Ang II type 1 receptor (AT1R), in the present study we investigated the effects of Ang II on choriocarcinoma cell migration/invasion in vitro using Transwell cell culture chambers. Ang II (10(-8) M) promoted migration and invasion by a choriocarcinoma cell line and augmented random cell mobility on checkerboard analysis. Immunoblotting showed Ang II to activate the phosphorylation of FAK and Akt in BeWo cells. Furthermore Ang II effects on cell migration were abolished by a selective AT1R antagonist and a phosphatidylinositol 3-kinase (PI3K) inhibitor. The present results suggest that Ang II-induced migration and invasion of choriocarcinoma cells probably involves PI3K following binding to the AT1R.