The potassium ion channel opener NS1619 inhibits proliferation and induces apoptosis in A2780 ovarian cancer cells
The potassium ion channel opener NS1619 inhibits proliferation and induces apoptosis in A2780 ovarian cancer cells
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钾离子通道开放剂 NS1619 抑制 A2780 卵巢癌细胞增殖并诱导细胞凋亡
DOI：
10.1016/j.bbrc.2008.07.161
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发表时间：
2008-10-17
影响因子：
3.1
通讯作者：
Ma, Ding
中科院分区：
文献类型：
--
作者：
Han, Xiaobing;Xi, Ling;Ma, Ding
多种类型的电压门控钾（K⁺）通道已被证明参与细胞增殖的调控。大电导钙激活钾通道（BK通道）可能在人类癌症的进展中起重要作用。为了探究BK通道在人卵巢癌细胞凋亡调控中的作用，观察了特异性BK通道激活剂NS1619对A2780细胞凋亡诱导的影响。用NS1619处理后，通过MTT法测定细胞增殖。通过细胞DNA的琼脂糖凝胶电泳和流式细胞术检测经NS1619预处理的A2780细胞的凋亡情况。我们的数据表明，NS1619以剂量和时间依赖的方式抑制A2780细胞的增殖（预处理48小时的半数抑制浓度IC₅₀ = 31.1 μM）并诱导凋亡。蛋白质印迹分析显示，NS1619的抗增殖作用与p53、p21和Bax表达增加有关。这些结果表明，BK通道在调节人卵巢癌细胞增殖中起重要作用，并可能以p53依赖的方式通过诱导p21（CiP1）表达来诱导凋亡。（c）2008爱思唯尔公司。保留所有权利。
Diverse types of voltage-gated potassium (K+) channels have been shown to be involved in regulation of cell proliferation. The maxi-conductance Ca2+-activated K+ channels (BK channels) may play an important role in the progression of human cancer. To explore the role of BK channels in regulation of apoptosis in human ovarian cancer cells, the effects of the specific BK channel activator NS 1619 on induction of apoptosis in A2780 cells were observed. Following treatment with NS1619, cell proliferation was measured by MTT assay. Apoptosis of A2780 cells pretreated with NS 1619 was detected by agarose gel electrophoresis of cellular DNA and flow cytometry. Our data demonstrate that NS1619 inhibits the proliferation of A2780 cells in a dosage and time dependent manner IC50 = 31.1 mu M, for 48 h pretreatment and induces apoptosis. Western blot analyses showed that the anti-proliferation effect of NS1619 was associated with increased expression of p53, p21, and Bax. These results indicate that BK channels play an important role in regulating proliferation of human ovarian cancer cells and may induce apoptosis through induction of p21(CiP1) expression in a p53-dependent manner. (c) 2008 Elsevier Inc. All rights reserved.