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缺氧微环境下钙信号介导鞘氨醇激酶1促进胶质瘤细胞增殖
引用本文:张贺,刘林华,石明,刘小山,唐焕文. 缺氧微环境下钙信号介导鞘氨醇激酶1促进胶质瘤细胞增殖[J]. 南方医科大学学报, 2015, 35(7): 1014
作者姓名:张贺  刘林华  石明  刘小山  唐焕文
作者单位:广东医学院公共卫生学院劳动卫生与环境卫生学教研室,广东 东莞,523808
基金项目:广东省自然科学基金(S2012040006314);广东医学院科研基金
摘    要:目的探讨缺氧微环境下鞘氨醇激酶1(SphK1)调控胶质瘤细胞增殖的分子机制。方法缺氧建立缺氧模型;RNA干扰技
术下调SphK1的表达,分别以real-time PCR及蛋白免疫印记方法检测SphK1在mRNA及蛋白水平上的表达;CCK-8检测胶质
瘤细胞增殖;流式细胞术检测细胞周期;Fluo-3/AM孵育,激光共聚焦显微镜检测细胞内Ca2+的动态变化。结果SphK1表达下
调可显著降低缺氧诱导的钙内流,并在缺氧条件下影响胶质瘤细胞增殖;钙通道激活剂OAG可减弱SphK1表达下调引起的细
胞增殖抑制。结论缺氧微环境下SphK1可通过对胞内钙离子的调控影响胶质瘤的增殖。


关 键 词:鞘氨醇激酶1  缺氧  钙信号  胶质瘤

Sphingosine kinase 1 promotes glioma cell proliferation under hypoxia via calcium signaling
ZHANG He,LIU Linhua,SHI Ming,LIU Xiaoshan,TANG Huanwen. Sphingosine kinase 1 promotes glioma cell proliferation under hypoxia via calcium signaling[J]. Journal of Southern Medical University, 2015, 35(7): 1014
Authors:ZHANG He  LIU Linhua  SHI Ming  LIU Xiaoshan  TANG Huanwen
Abstract:Objective To investigate the role of sphingosine kinase 1 (SphK1) in regulating the proliferation of hypoxia-exposed
glioma cells in vitro and explore the possible molecular mechanisms. Methods Human glioblastoma U87MG cells was
transfected with specific small interfering RNA (siRNA) constructs targeting SphK1, and the efficiency of SphK1 knockdown
was validated by real-time PCR and Western blotting. The cells transfected with SphK1 siRNA and with a negative control
siRNA were then exposed to 3% oxygen or 150 μmol/L CoCl2 to induce hypoxia. The cell proliferation and cell cycle changes
following the exposure were evaluated with the Cell Counting Kit-8 and flow cytometry, respectively, and the intracellular Ca2+
changes were monitored using Flou-4/AM under an inverted laser scanning confocal microscope. Results SphK1 knockdown
significantly reduced hypoxia-induced calcium reflux and suppressed the cell proliferation. Application of OAG, an activator
of calcium channels, however, obviously enhanced the cell proliferation under hypoxia. Conclusion SphK1 promotes the
proliferation of glioma cells under hypoxia via regulating calcium signaling.
Keywords:sphingosine kinase 1  hypoxia  calcium signaling  glioma
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