人参总皂甙及其主要成分对白血病细胞组蛋白乙酰化修饰的影响及β-catenin在此过程中发挥的作用

项目名称： 人参总皂甙及其主要成分对白血病细胞组蛋白乙酰化修饰的影响及β-catenin在此过程中发挥的作用

项目编号： No.31271368

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 陈地龙

作者单位： 重庆医科大学

项目金额： 60万元

中文摘要： 我们的前期研究结果发现，人参提取物人参总皂甙（TSPG）对白血病细胞的增殖抑制、诱导分化和促进凋亡的作用明确且显著，基因表达谱分析显示其作用涉及众多信号通路，细胞生物学验证中发现β-catenin的含量下降和功能下调最为明显。已知组蛋白的修饰影响染色质的结构改变，从而影响转录因子和RNA聚合酶的结合，使得同一机制可同时决定众多基因的转录，且β-catenin为组蛋白乙酰化修饰蛋白的募集提供平台。因此我们认为在TSPG对白血病细胞的增殖抑制和诱导分化过程中β-catenin发挥着关键作用，并通过影响组蛋白的乙酰化及其导致的染色质变构而控制其他重要蛋白质的转录和信号通路的活性。本项目拟设计实验证明之。本项目的实施，可望初步阐明TSPG对白血病细胞作用的新机制，为其临床应用奠定基础。同时，针对新发现的作用机制，可利用小分子化合物进行抑制等方法进行治疗。此外，机制的阐明也有利于中药应用的国际化。

中文关键词： 人参皂甙Rh2(S)；白血病；HDAC6；乙酰化；β-catenin

英文摘要： Our previous study showed that total saponins of Panax ginseng (TSPG) inhibited the proliferation of leukemia cells, induced their differentiation, and promoted their apoptosis. Gene expression array analysis showed that a broad spectrum of cell signaling pathways was involved in these functions, among which the content of β-catenin decreased significantly, and its function lowered dramatically. It was widely known that histones modification affects the structure of chromatin, thereby, control the binding of transcription factors to RNA polymerase, this make it likely that one mechanism control the transcription of many genes. β-catenin provides a platform for the acetylation modification of histones. Therefore, we hypothesized that TSPG exerted its function on leukemia cells through β-catenin, and thus affects many important gene transcription and signaling pathway through histone acetylation and chromatin alteration. This project aims to testify the hypothesis. The implementation of this project may demonstrate a new mechanism by which TSPG functions on leukemia cells, and at the same time, the new-fond mechanism may serve as therapeutic target for small molecules compound. In addition, the demonstration of mechanism may be in favor of the internationalization of traditional Chinese medicine.

英文关键词： Ginsenoside Rh2(S)；leukemia；HDAC6；acetylation；β-catenin