细胞内胆固醇代谢在前列腺癌神经内分泌转化中的变化及意义  

Changes of intracellular cholesterol metabolism in neuroendocrine differentiation of prostate cancer and their significance

作　　者：王蓉[1] 吴开杰[2] 牛刚[1] 王新阳[2] 贺大林[2] 

机构地区：[1]西安交通大学第一附属医院医学影像科,陕西西安710061 [2]西安交通大学第一附属医院泌尿外科,陕西西安710061

出　　处：《中华男科学杂志》2013年第3期199-204,共6页National Journal of Andrology

基　　金：教育部留学回国人员科研启动基金(2008);高等学校博士学科点专项科研基金新教师类课题(200806981028);陕西省科技攻关项目(2008K09-09)~~

摘　　要：目的:建立前列腺癌雄激素非依赖进展过程中的神经内分泌转化(NED)体外细胞模型,分析前列腺癌NE细胞转化时细胞内胆固醇代谢及其调控可能的变化及意义。方法:去雄激素诱导建立前列腺癌LNCaP细胞NE模型,通过细胞形态学观察、蛋白印迹检测多种NE标记物(SgⅢ、NSE、CgA)表达、体外细胞增殖实验检测NE的发生;利用免疫荧光染色检测细胞内胆固醇和SgⅢ的表达及分布;利用半定量RT-PCR检测多种参与胆固醇合成、摄取相关蛋白基因(LDL-R、SREBP-1、SREBP-2)的表达。结果:去除雄激素后体外培养,LNCaP细胞胞体缩小,轴突增长,呈NE样改变;SgⅢ、NSE、CgA等多种NE标记物表达上调,并随着时间延长逐渐增多;同时细胞增殖能力显著降低(P<0.05)。NE转化后的LNCaP细胞内胆固醇分布呈现明显的轴突末端聚集趋势,但表达量并无显著改变,相应的细胞内参与胆固醇合成、摄取相关蛋白基因的表达也无显著性差异(P>0.05)。结论:短期去雄激素体外培养可成功诱导雄激素依赖的前列腺癌LNCaP细胞发生NED,NED后的细胞内胆固醇分布发生显著的轴突末端聚集趋势,以增强细胞内多种神经内分泌颗粒的形成。Objective： To explore the roles of intracellular cholesterol metabolism in neuroendocrine （NE） differentitaion of prostate cancer based on an androgen-independent prostate cancer NE cell model induced by androgen deprivation. Methods ： LNCaP cells were cultured in androgen-depleted medium, and NE phenotypes were identified by observing the changes in cell morphology, molecular markers （ Sg Ⅲ, NSE and CgA） and cell proliferation. The expression and distribution of cholesterol and Sg Ⅲwere determined by immunofluorescence staining. The expressions of the key genes LDL-R, SREBP-1 and SREBP-2 involved in cholesterol synthesis and uptake were detected by semi-quantitative RT-PCR. Results： The LNCaP cells showed shrinking bodies and extending axons after androgen deprivation, and all the molecular markers, such as Sg m, NSE and CgA, significantly increased in a time-dependent man- ner, while the cell proliferation was obviously inhibited （P 〈 O. 05 ）. The cholesterol distribution in the LNCaP cells after NE differenti- ation presented remarkable aggregation at the axon terminals. However, there were no significant differences in the expression of cho- lesterol between the two types of cells, nor in the changes of the expressions of key genes LDL-R, SREBP-1 and SREBP-2 involved incholesterol synthesis and uptake （ P 〉 0.05 ）. Conclusion ： Transient androgen depletion could successfully induce NE differentiation of LNCaP cells, and the intracellular cholesterol could re-distribute into axon terminals to enhance the formation of neurosecretory gran ules.

关 键 词：前列腺癌 雄激素非依赖 神经内分泌转化 胆固醇代谢 

分 类 号：R737.25[医药卫生—肿瘤] R730.231[医药卫生—临床医学]