SKF95365 induces apoptosis and cell-cycle arrest by disturbing oncogenic Ca(2+) signaling in nasopharyngeal carcinoma cells.
SKF95365 induces apoptosis and cell-cycle arrest by disturbing oncogenic Ca(2+) signaling in nasopharyngeal carcinoma cells.
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SKF95365 通过干扰鼻咽癌细胞中的致癌 Ca(2 ) 信号传导来诱导细胞凋亡和细胞周期停滞。
DOI：
10.2147/ott.s92005
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发表时间：
2015
影响因子：
4
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Zhang J;Wei J;He Q;Lin Y;Liang R;Ye J;Zhang Z;Li Y
钙池操纵的钙离子（Ca2+）进入的异常调节促进人类恶性肿瘤的进展。在此之前，我们报道了阻断钙池操作的Ca 2+进入抑制表皮生长因子（EGF）刺激的鼻咽癌（NPC）细胞迁移和远处转移。然而，药理学阻断剂对NPC细胞中其他Ca2+信号调节的恶性特征的影响仍然知之甚少。我们研究了SKF96365，一种钙池操纵的钙通道抑制剂，对两种NPC细胞系EGF启动的钙信号的影响。我们在体外测定了SKF96365对细胞增殖、集落形成、凋亡和细胞周期状态的影响。我们进一步阐明了SKF96365在异种移植荷瘤小鼠中的抗肿瘤活性。发现SKF96365干扰了毒胡萝卜素（TG）刺激的内质网Ca~（2+）释放和随后的Ca~（2+）内流。SKF96365单独刺激Ca 2+反应仅仅是由于内质网释放的Ca 2+。SKF96365促进细胞死亡，抑制集落形成，诱导细胞凋亡和细胞周期阻滞，同时减弱EGF诱导的Ca2+信号。此外，我们证实SKF96365减少NPC异种移植物的生长，同时激活caspase-7相关的凋亡途径。SKF96365通过阻断鼻咽癌细胞内致癌性Ca2+信号转导而发挥多种抗肿瘤活性。
Aberrant modulation of store-operated calcium ions (Ca2+) entry promotes the progression of human malignancies. Previously, we reported that the blockage of store-operated Ca2+ entry inhibited epidermal growth factor (EGF)-stimulated migration and distant metastasis in nasopharyngeal carcinoma (NPC) cells. However, the effects of pharmacological blocker on other Ca2+ signaling-regulated malignant characteristics in NPC cells remained poorly understood. We examined the effects of SKF96365, an inhibitor of store-operated Ca2+ channel, on EGF-launched Ca2+ signaling in two NPC cell lines. We determined the effects of SKF96365 on cell proliferation, colony formation, apoptosis, and cell-cycle status in vitro. We further elucidated the antitumor activity of SKF96365 in xenograft-bearing mice. It was found that SKF96365 disturbed the thapsigargin (TG)-stimulated Ca2+ release from endoplasmic reticulum and the subsequent Ca2+ influx. SKF96365 alone stimulated Ca2+ responses merely due to endoplasmic reticulum-released Ca2+. SKF96365 promoted cell mortality, inhibited colony formation, and induced apoptosis and cell-cycle arrest, while blunting the EGF-evoked Ca2+ signaling. Furthermore, we confirmed that SKF96365 reduced NPC xenograft growth while activating caspase-7-related apoptotic pathway. SKF96365 exerts multiple antitumor activities through the distraction on the oncogenic Ca2+ signaling transduction in NPC cells.