线粒体铁蛋白过表达抑制神经肿瘤细胞的增长与细胞铁代谢及细胞周期蛋白表达相关  

Overexpression of mitochondrial ferritin inhibits the tumour cell proliferation by regulation of cellular iron mechanism and the expression of cyclins

作　　者：史方方[1] 张娜[1] 关鹏[1] 高志国[1] 范婧琪[1] 常彦忠[1] 石振华段相林 

机构地区：[1]河北师范大学生命科学学院,石家庄050024

出　　处：《解剖学报》2013年第2期214-218,共5页Acta Anatomica Sinica

基　　金：国家自然科学基金资助项目(31271146);河北省应用基础研究计划资助项目(10966120D)

摘　　要：目的探讨过表达线粒体铁蛋白(MtFt)抑制成神经母细胞瘤SH-SY5Y细胞的增殖机制。方法以过表达MtFt的成神经母细胞瘤细胞MtFt-SY5Y为实验模型,野生型SH-SY5Y和pcDNA3.1-SY5Y(空质粒对照)为实验对照,运用流式细胞术、Western blotting技术等检测了MtFt对SH-SY5Y肿瘤细胞增殖的影响及铁代谢相关蛋白转铁蛋白受体1(TfR1),铁蛋白和细胞周期相关蛋白(cyclin)及其依赖性激酶(CDK)、cyclinD1、CDK4、cyclinE、CDK2的表达变化。结果 MtFt过表达通过调节细胞内铁代谢显著抑制了神经肿瘤细胞SH-SY5Y的增殖,与对照组相比,MtFt-SY5Y细胞增殖速度慢了近4倍。MtFt造成了细胞质内铁缺乏,TfR1表达显著上调,而铁蛋白H亚基(H-ferritin)显著下调。同时cyclinD1与CDK2蛋白表达显著降低,cyclinE蛋白表达显著上升,CDK4蛋白表达无显著性差异。结论 MtFt过表达能够显著抑制神经肿瘤细胞的生长,其机制可能是通过调节细胞内铁代谢,从而影响细胞周期相关蛋白及其周期蛋白激酶的表达。Objective To study the mechanism of overexpression of mitochondrial ferritin （MtFt） for inhibiting neuroblastoma cell proliferation. Method MtFt-SY5Y cells were selected as the experimental model and SH-SY5Y and peDNA3. 1-SY5Y cells were used as control group. The effects of overexpression of MtFt on SH-SY5Y cells proliferation, iron metabolism related protein transferrin receptorl （TfR1） and ferritin, cyclins（ cyclinD1, cyclinE ） and cyclin dependant kinases（CDK2, CDK4） were tested by flow cytometry and Western bloting. Result Overexpression of MtFt inhibited markedly tumour cell proliferation by regulation of iron metabolism and the expression of cyclins and cyclin dependant kinase. The proliferation speed of MtFt-SYSY cells was 4 times slower than that of the control group. MtFt caused the cytoplasm iron deficiency and transferrin receptorl （TfR1） upregulation, and H-ferritin downregulation markedly respectively. Meanwhile, eyclinD1 and CDK2 downregulated significantly and cyclinE upregulated significantly. The expression of CDK4 decreased but no significant difference compared with control group. Conclusion Overexpression of MtFt inhibits the tumour cell proliferation markedly. The mechanism may be caused by regulation of cellular iron metabosism and the expression of cyclins and cyclin dependent kinase （CDK） which further arrest cell cycle.

关 键 词：线粒体铁蛋白 铁代谢 细胞增殖 细胞周期蛋白 流式细胞术 免疫印迹法 

分 类 号：R739.4[医药卫生—肿瘤]