The blocking of capacitative calcium entry by 2-aminoethyl diphenylborate (2-APB) and carboxyamidotriazole (CAI) inhibits proliferation in Hep G2 and Huh-7 human hepatoma cells
The blocking of capacitative calcium entry by 2-aminoethyl diphenylborate (2-APB) and carboxyamidotriazole (CAI) inhibits proliferation in Hep G2 and Huh-7 human hepatoma cells
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DOI：
10.1016/j.ceca.2004.04.004
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发表时间：
2004-12-01
期刊：
影响因子：
4
通讯作者：
Capiod, T
中科院分区：
文献类型：
--
作者：
Enfissi, A;Prigent, S;Capiod, T
钙进入是调节某些类型癌症的增殖表型过程的组成部分。在非兴奋性细胞中，电容性钙内流（CCE）和非电容性钙内流（NCCE）被认为是Ca2+流入细胞的主要途径。因此。阻止钙进入可能会阻止正常和病理性细胞增殖，并且有证据表明阻止钙进入的分子也具有抗增殖特性。羧酰胺三唑 (CAI) 是一种新型非电压依赖性钙进入抑制剂，已在体外和体内模型系统中显示出这种特性。我们使用 Hep G2 和 Huh-7 人肝癌细胞来研究钙进入阻滞剂对细胞增殖的影响。 CAI (10 muM) 和 2-APB (20 muM) 完全阻断毒胡萝卜素处理的 Huh-7 中的 CCE，并且 CAI 和 2-APB 抑制细胞增殖，IC50 分别为 4.5 和 43 muM。在没有外部 Ca2+ 且存在 CAI 或 2-APB 的情况下，由 10% FCS 触发的 [Ca2+](i) 增加的平台期被消除。因此，我们认为 CCE 是参与调节细胞增殖过程的主要途径。 (C) 2004 Elsevier Ltd. 保留所有权利。
Calcium entry is a component of the processes regulating the proliferative phenotype of some types of cancer. In non-excitable cells, capacitative calcium entry (CCE) and non-capacitative calcium entry (NCCE) are thought to be the main pathways of Ca2+ influx into cells. Thus. blocking calcium entry may prevent normal and pathological cell proliferation and there is evidence to suggest that molecules blocking calcium entry also have antiproliferative properties. Carboxyamidotriazole (CAI), a novel inhibitor of the non-voltage-dependent calcium entry has been shown to have such properties in model systems in vitro and in vivo. We used Hep G2 and Huh-7 human hepatoma cells to investigate the effects of calcium entry blockers on cell proliferation. CAI (10 muM) and 2-APB (20 muM) completely blocked CCE in thapsigarain-treated Huh-7, and CAI and 2-APB inhibited cell proliferation with IC50 of 4.5 and 43 muM, respectively. The plateau phase of the [Ca2+](i) increases triggered by 10% FCS were abolished in the absence of external Ca2+ and in the presence of CAI or 2-APB. We, therefore, suggest that CCE is the main pathway involved in regulation of the processes leading to cell proliferation. (C) 2004 Elsevier Ltd. All rights reserved.