Inhibition of proliferation of MCF-7 breast cancer cells by a blocker of Ca2+-permeable channel
Inhibition of proliferation of MCF-7 breast cancer cells by a blocker of Ca2+-permeable channel
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DOI：
10.1016/s0143-4160(97)90107-x
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发表时间：
1997-08-01
期刊：
影响因子：
4
通讯作者：
Kojima, I
中科院分区：
文献类型：
--
作者：
Nie, L;Oishi, Y;Kojima, I
在 MCF-7 乳腺癌细胞中，胰岛素样生长因子 1 (IGF-1) 通过激活电压无关的钙渗透性通道来增加细胞的钙渗透性。 IGF-1 还诱导这些细胞中细胞质游离钙浓度的振荡升高。抗过敏化合物曲尼司特以剂量依赖性方式降低 IGF-1 增强的钙渗透性，并阻止细胞质游离钙浓度的振荡升高。曲尼司特不影响 IGF-1 激活的早期细胞内信号，包括受体自身磷酸化、Ras 激活、丝裂原激活蛋白激酶和磷脂酰肌醇 3-激酶。 Tranilast 抑制 IGF-1 诱导的 [H-3]-胸苷掺入、DNA 含量和细胞数量的增加。 [H-3]-胸苷掺入和DNA含量的ID50约为10μM。曲尼司特的抑制作用是可逆的，并且不影响细胞活力。曲尼司特处理增加了 G(1) 期细胞数量，表明该化合物诱导 G(1) 停滞。曲尼司特还降低了视网膜母细胞瘤蛋白的磷酸化。这些结果表明曲尼司特通过阻止钙进入来抑制 MCF-7 细胞中 IGF-1 诱导的细胞生长。
In MCF-7 breast cancer cells, insulin-like growth factor-1 (IGF-1) increased the calcium-permeability of the cells by activating a voltage-independent calcium-permeable channel. IGF-1 also induced oscillatory elevation of cytoplasmic free calcium concentration in these cells. An anti-allergic compound, tranilast, reduced the calcium-permeability augmented by IGF-1 in a dose-dependent manner and blocked the oscillatory elevation of cytoplasmic free calcium concentration. Tranilast did not affect early intracellular signals activated by IGF-1, including receptor autophosphorylation, activations of Ras, mitogen-activated protein kinase and phosphatidylinositol 3-kinase. Tranilast inhibited increases in [H-3]-thymidine incorporation, DNA content and cell number induced by IGF-1. The ID50 for [H-3]-thymidine incorporation and DNA content were about 10 mu M. The inhibitory effect of tranilast was reversible, and cell viability was not affected. Treatment with tranilast increased the number of cells in the G(1) phase suggesting that this compound induced G(1) arrest. Tranilast also reduced the phosphorylation of the retinoblastoma protein. These results indicate that tranilast inhibits the IGF-1-induced cell growth in MCF-7 cells by blocking calcium entry.