Nifedipine promotes the proliferation and migration of breast cancer cells.
Nifedipine promotes the proliferation and migration of breast cancer cells.
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硝苯地平促进乳腺癌细胞增殖和迁移
DOI：
10.1371/journal.pone.0113649
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Gu YC
中科院分区：
文献类型：
--
作者：
Guo DQ;Zhang H;Tan SJ;Gu YC
硝苯地平作为钙通道阻滞剂（CCB）被广泛用于治疗心绞痛和高血压，但在刺激癌症的风险方面存在争议。在这项研究中，我们证明了硝苯地平促进乳腺癌细胞在体内和体外的增殖和迁移。然而，另一种钙通道阻滞剂维拉帕米没有产生类似的效果。硝苯地平和高浓度KCl均不能改变MDA-MB-231细胞中的[Ca2+]i，提示硝苯地平的作用与钙通道无关。此外，硝苯地平降低miRNA-524-5p，导致脑蛋白I3 （BRI3）上调。Erk通路因此被激活，导致乳腺癌细胞的增殖和迁移。抑制BRI3逆转了硝苯地平对乳腺癌的促进作用。综上所述，硝苯地平通过miRNA-524-5p-BRI3-Erk通路轴刺激乳腺癌细胞的增殖和迁移，而不依赖于其钙通道阻断活性。我们的研究结果强调硝苯地平而不是维拉帕米有利于乳腺癌的生长和转移，敦促临床在给高血压和乳腺癌并存的女性以及有乳腺癌倾向的高血压患者开硝苯地平时要谨慎。
Nifedipine is widely used as a calcium channel blocker (CCB) to treat angina and hypertension,but it is controversial with respect the risk of stimulation of cancers. In this study, we demonstrated that nifedipine promoted the proliferation and migration of breast cancer cells both invivo and invitro. However, verapamil, another calcium channel blocker, didn’t exert the similar effects. Nifedipine and high concentration KCl failed to alter the [Ca2+]i in MDA-MB-231 cells, suggesting that such nifedipine effect was not related with calcium channel. Moreover, nifedipine decreased miRNA-524-5p, resulting in the up-regulation of brain protein I3 (BRI3). Erk pathway was consequently activated and led to the proliferation and migration of breast cancer cells. Silencing BRI3 reversed the promoting effect of nifedipine on the breast cancer. In a summary, nifedipine stimulated the proliferation and migration of breast cancer cells via the axis of miRNA-524-5p-BRI3–Erk pathway independently of its calcium channel-blocking activity. Our findings highlight that nifedipine but not verapamil is conducive for breast cancer growth and metastasis, urging that the caution should be taken in clinic to prescribe nifedipine to women who suffering both hypertension and breast cancer, and hypertension with a tendency in breast cancers.
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影响因子：
64.8
作者：
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通讯作者：
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通讯作者：
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通讯作者：
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影响因子：
4
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通讯作者：
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影响因子：
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