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首页> 外文期刊>Life sciences >Amlodipine, a Ca2+ channel blocker, suppresses phosphorylation of epidermal growth factor receptor in human epidermoid carcinoma A431 cells.
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Amlodipine, a Ca2+ channel blocker, suppresses phosphorylation of epidermal growth factor receptor in human epidermoid carcinoma A431 cells.

机译：氨氯地平是一种Ca2 +通道阻滞剂，可抑制人表皮样癌A431细胞中表皮生长因子受体的磷酸化。

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AIMS: Amlodipine, a dihydropyridine Ca(2+) channel blocker, inhibits the proliferation of human epidermoid carcinoma A431 cells in vitro and in vivo. This study examined the underlying mechanism of this antiproliferative effect in relation to epidermal growth factor receptor (EGFR) signaling. MAIN METHODS: The tyrosine phosphorylated active state of EGFR in A431 cells incubated with the test agents was evaluated by western blot with anti-phosphotyrosine antibody. EGFR phosphorylation levels in A431 xenograft tumors were assessed by immunostaining of matrigel plug sections and western blotting for phosphoEGFR in A431 xenograft tumor homogenates. KEY FINDINGS: In vitro treatment of exponentially growing A431 cells with amlodipine decreased the tyrosine phosphorylation states of EGFR. Amlodipine also suppressed the EGF-stimulated phosphorylation of EGFR and a membrane scaffolding protein, caveolin-1, in serum-starved A431 cells. Amlodipine attenuated the EGF-stimulated phosphorylation of EGFR coimmunoprecipitated with caveolin-1 without affecting the EGFR/caveolin-1 interaction. Crosslinking experiments showed that amlodipine also suppressed the EGF-stimulated phosphorylation of EGFR predimers. Addition of cholesterol abolished these inhibitory effects of amlodipine plus its inhibition of cell growth. Furthermore, treatment of mice with amlodipine (10mg/kg/dayx7days, i.p.) decreased the levels of phosphorylated EGFR in A431 xenograft tumors. SIGNIFICANCE: The results indicated that amlodipine inhibits tyrosine phosphorylation of EGFR in vitro and in vivo, possibly via modulating cholesterol-rich, caveolin-1-containing membrane microdomains.
机译：目的：氨氯地平，一种二氢吡啶Ca（2+）通道阻滞剂，在体外和体内抑制人表皮样癌A431细胞的增殖。这项研究检查了这种抗增殖作用与表皮生长因子受体（EGFR）信号传导有关的潜在机制。主要方法：用抗磷酸酪氨酸抗体通过western blot评估与试验药物一起孵育的A431细胞中EGFR的酪氨酸磷酸化活性状态。通过Matrigel塞节的免疫染色和Western印迹法对A431异种移植肿瘤匀浆中的EGFR进行评估，以评估A431异种移植肿瘤中的EGFR磷酸化水平。主要发现：用氨氯地平体外处理成倍增长的A431细胞可降低EGFR的酪氨酸磷酸化状态。氨氯地平还可以抑制血清饥饿的A431细胞中EGF刺激的EGFR磷酸化和膜支架蛋白小窝蛋白1。氨氯地平减弱了由EGF刺激的与小窝蛋白1共免疫沉淀的EGFR的磷酸化，而没有影响EGFR /小窝蛋白1的相互作用。交联实验表明，氨氯地平还可以抑制EGF刺激的EGFR前体的磷酸化。胆固醇的添加消除了氨氯地平的这些抑制作用以及对细胞生长的抑制作用。此外，用氨氯地平（10mg / kg /天×7天，腹腔注射）治疗小鼠降低了A431异种移植肿瘤中磷酸化EGFR的水平。意义：结果表明氨氯地平在体外和体内均可抑制EGFR酪氨酸磷酸化，可能是通过调节富含胆固醇的，含有Caveolin-1的膜微区来实现的。

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