Sensitization of human colon cancer cells to sodium butyrate-induced apoptosis by modulation of sphingosine kinase 2 and protein kinase D.
Sensitization of human colon cancer cells to sodium butyrate-induced apoptosis by modulation of sphingosine kinase 2 and protein kinase D.
复制标题
通过调节鞘氨醇激酶 2 和蛋白激酶 D 使人结肠癌细胞对丁酸钠诱导的细胞凋亡敏感。
DOI：
10.1016/j.yexcr.2011.10.006
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
邹飞
中科院分区：
文献类型：
--
作者：
邹飞
鞘氨醇激酶（SphKs）被认为是调节细胞增殖和凋亡的重要蛋白。在SphK的两种亚型（SphK 1和SphK 2）中，人们对SphK 2的功能知之甚少。丁酸钠（NaBT）已被确定为一种有前途的化疗药物，但其作用的确切机制尚不清楚。在这项研究中，我们研究了SphK 2在NaBT诱导的HCT 116结肠癌细胞凋亡中的作用。结果表明，NaBT处理后SphK 2从细胞核转位至细胞质，并在细胞质中聚集，同时仅发生轻度凋亡。然而，SphK 2的下调导致敏化的细胞凋亡，SphK 2的过表达导致甚至更轻的细胞凋亡;这些强烈表明SphK 2在NaBT诱导的细胞凋亡中的抑制作用。在使用siRNA敲低蛋白激酶D（PKD）（另一种据报道在细胞增殖/凋亡过程中起关键作用的蛋白质）后，观察到NaBT处理后SphK 2的细胞质积累的阻断和敏化凋亡。本研究提示，PKD和SphK 2可能构成了肿瘤细胞对化疗药物的抵抗机制，如HCT 116结肠癌细胞对NaBT的抵抗，这两种蛋白可能成为设计新的肿瘤治疗药物的分子靶点。
Sphingosine kinases (SphKs) have been recognized as important proteins regulating cell proliferation and apoptosis. Of the two isoforms of SphK (SphK1 and SphK2), little is known about the functions of SphK2. Sodium butyrate (NaBT) has been established as a promising chemotherapeutic agent, but the precise mechanism for its effects is unknown. In this study, we investigated the role of SphK2 in NaBT-induced apoptosis of HCT116 colon cancer cells. The results indicated that following NaBT treatment SphK2 was translocated from the nucleus to the cytoplasm, leading to its accumulation in the cytoplasm; in the meantime, only mild apoptosis occurred. However, downregulation of SphK2 resulted in sensitized apoptosis, and overexpression of SphK2 led to even lighter apoptosis; these strongly indicate an inhibitory role of SphK2 in cell apoptosis induced by NaBT. After knocking down protein kinase D (PKD), another protein reported to be critical in cell proliferation/apoptosis process, by using siRNA, blockage of cytoplasmic accumulation of SphK2 and sensitized apoptosis following NaBT treatment were observed. The present study suggests that PKD and SphK2 may form a mechanism for the resistance of cancer cells to tumor chemotherapies, such as HCT116 colon cancer cells to NaBT, and these two proteins may become molecular targets for designation of new tumor-therapeutic drugs.
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影响因子：
11.5
作者：
Song, Libing;Xiong, Huaping;Li, Mengfeng
通讯作者：
Li, Mengfeng
影响因子：
13.8
作者：
K. Weis
通讯作者：
K. Weis
影响因子：
4.8
作者：
Kawamori, Toshihiko;Kaneshiro, Tatsuya;Obeid, Lina M.
通讯作者：
Obeid, Lina M.
DOI：
10.1016/j.bbrc.2006.02.070
发表时间：
2006-04-21
影响因子：
3.1
作者：
Akao, Y;Banno, Y;Nozawa, Y
通讯作者：
Nozawa, Y
影响因子：
11.2
作者：
Bandyopadhyay, D;Mishra, A;Medrano, EE
通讯作者：
Medrano, EE