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鞘氨醇激酶1参与依托泊苷抑制人乳腺癌MDA-MB-231细胞增殖、迁移的研究
引用本文:续旭,;辛翠燕,;任树昱. 鞘氨醇激酶1参与依托泊苷抑制人乳腺癌MDA-MB-231细胞增殖、迁移的研究[J]. 国外医学:分子生物学分册, 2009, 0(3): 243-247
作者姓名:续旭,  辛翠燕,  任树昱
作者单位:[1]深圳大学生命科学学院,广东省深圳市518060; [2]Institute of Pharmacology,University Bern,CH-3010 Bern,Switzerland
摘    要:目的利用抑制乳腺癌MDA-MB-231细胞中SK-1基因表达,结合依托泊苷对细胞增殖的影响,研究乳腺癌的治疗新方法。方法将依托泊苷分别处理野生型及SK-1敲除型MDA-MB-231细胞,^3H-TdR掺入法分析细胞增殖,Transwell法分析细胞迁移,Western印迹检测SK-1蛋白表达及细胞周期检验点相关信号因子的蛋白表达,RT-PCR检测细胞内SK-1的mRNA表达量。结果依托泊苷在较高剂量时,MDA-MB-231细胞存活率明显下降,但依托泊苷却呈浓度依赖性促进乳腺癌细胞SK-1 mRNA及蛋白水平表达,将SK-1敲除,细胞迁移率下降,而且可以增强G1期各抑癌基因的激活或高表达,使细胞周期阻滞。结论SK-1基因敲除有效增强肿瘤细胞对化疗药物的敏感性。

关 键 词:鞘氨醇激酶1  依托泊苷  MDA-MB-231细胞  细胞周期检验点

Regulative Effects of Sphingosine Kinase I and Etoposide on Proliferation and Migration of MDA-MB-231 Human Breast Cancer Cells
Affiliation:XU Xu, XIN Cuiyan, REN Shuyu(1. College of Life Science, Shenzhen University, Shenzhen, Guangdong, 518060, China;2.Institute of Pharmacology, University Bern, CH-3010 Bern, Switzerland)
Abstract:Objective This study was aimed to explore novel therapeutics for breast cancer, by combining knockout of sphingosine kinase 1(SK-1) with inhibitory effect of etoposide on cell prolif- eration of human breast cancer cell line MDA-MB-231. Methods Cell proliferation ability was measured by 3H-TdR and the cell migration was performed by Transwell. Western blot assay was used to detect expression of SK-1 and related signal factors at cell-cycle checkpoints, and RT-PCR was performed to observe the levels of SK-1 mRNA. Results Etoposide inhibited cell proliferation of human breast cancer cell MDA-MB-231 at a relatively high dose, but upregulated the expression and mRNA of SK-1 in a dose-dependent manner. SK-1 knockout, in combination with etopside, inhibited migration of MDA-MB-231 cells, and markedly increased expression of signal genes related to G1 arrest of cell-cycle checkpoint. Conclusion Knockout of SK-1 can enhance the sensitivity of human breast cancer cells to chemotherapeutics.
Keywords:sphingosine kinase 1 (SK-1)  etoposide  human breast cancer cells MDA-MB-231  cell cycle checkpoint
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