茶色素对叙利亚地鼠胚胎正常细胞和癌前细胞生长选择性作用的机制研究  

Mechanism study of tea pigment on the selective against the colony growth of preneoplastic and normal Syrian Hamster embryo cells

作　　者：焦振泉[1] 叶宏[2] 郭云昌[3] 徐勇[4] 

机构地区：[1]中国疾病预防控制中心公共卫生管理处,北京100050 [2]中国疾病预防控制中心传染病预防控制所 [3]中国疾病预防控制中心营养与食品安全所 [4]美国印第安那大学医学院

出　　处：《卫生研究》2008年第3期294-298,共5页Journal of Hygiene Research

基　　金：国家自然科学基金项目(No.30400357)

摘　　要：目的利用叙利亚地鼠胚胎细胞(SHE)混合培养模型,研究不同剂量的红茶提取物活性物质茶色素(TP)对SHE正常细胞和癌前细胞生长、增殖、凋亡及相关调控基因表达的影响。方法以0μg/ml的TP为对照组,通过细胞生长实验、原位细胞增殖实验、细胞凋亡实验、Microarray实验来研究不同浓度的TP(0.5、1、5、10和50μg/ml)对单独培养的HE正常细胞和癌前细胞及混和培养模型SHE癌前细胞凋亡、增殖和相关调控基因表达的作用。结果TP促进SHE正常细胞的生长和增殖,对其凋亡没有影响;TP抑制SHE癌前细胞的生长和增殖,促进癌前细胞的凋亡;TP抑制混合培养模型中SHE癌前细胞的生长和增殖,促进其凋亡;TP对于细胞凋亡的调控可能通过Caspase3、Caspase8、p53、bad、bax、GADD45等上调基因及mdm2基因下调来实现;TP对于细胞增殖的调控可能通过阻滞细胞周期G2期实现。结论TP通过促进细胞凋亡直接或者通过促进正常细胞的增殖间接来抑制癌前细胞向肿瘤的转变,这种选择性作用可能与TP的抑癌机制有关。Objective To use co-cuhures of SHE normal and preneoplastic cells in order to study the chemopreventive effects of doses of tea pigment （TP） from black tea on growth, proliferation, apoptosis and related regulation gene expression of normal and preneoplastic SHE cells. Methods The different dose of TP（ 0,0.5,1,5,10 and 50/μg/ml）were used to treat the cells and the SHE cells growth growth assay and in situ apoptosis assay, in situ proliferation assay and microarray assay were used to determine the growth , proliferation , apoptosis, regulation gene expression of SHE preneoplastic cells. Results TP induced the colony growth and proliferation of SHE normal cells and had no effect on its apoptosis. TP suppressed the growth and proliferation of SHE preneoplastic cells and induced its apoptosis. TP suppressed the growth and proliferation of SHE preneoplastic cells and induced its apoptosis in co-cultures. The pathways of cell apoptosis were up-regulated through the Caspase3, Casp ase8, P53, bad, bax, GADD4 and down-regulated mdm2 signal pathways, and the pathways of cell proliferation were regulated through blockage of G2 phase of cell cycle. Conclusion The suppression of transferring from preneoplastic cells to tumor cells was both directly through inducing preneoplastic cell apoptosis and indirectly through induced surrounding normal cells proliferation. This selective effect should be helpful to clarifying mechanism of TP＇s chempreventive effect on tumorigenecity in rodent assays.

关 键 词：茶色素 叙利亚地鼠胚胎细胞 细胞凋亡 细胞增殖 调控基因表达 肿瘤 

分 类 号：R730.1[医药卫生—肿瘤] TS272[医药卫生—临床医学]