紫草素干预白血病细胞生长的巯基修饰机制研究

项目名称： 紫草素干预白血病细胞生长的巯基修饰机制研究

项目编号： No.81460566

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 张波

作者单位： 石河子大学

项目金额： 45万元

中文摘要： 一些含紫草方剂具有治疗白血病及防止复发的作用，这种作用被认为与紫草凉血活血的功效密切相关。一般认为白血病细胞的诱导分化与凋亡是药物化疗的两种机制，但后来研究发现二者在不同层次与细胞内氧化还原态变化有关。近年来，我们和其它研究者陆续发现白血病细胞对紫草素敏感性远高于其它肿瘤细胞株，且紫草素具有明显的巯基反应特性和氧化还原通路的调控特性，其既诱导白血病细胞分化又能引发凋亡。紫草素通过怎样的机制来发挥这些作用成为急需探索的一个重要理论问题。本项目拟利用前期工作建立的白血病细胞分化/凋亡评价模型，在细胞氧化还原态变化及巯基修饰性上对紫草素抑制白血病细胞作用的可能机制进行系统研究。本项目的突破不但有助于深入理解白血病细胞对紫草素极其敏感的化学实质，而且是对氧化还原调控理论的丰富和补充。

中文关键词： 巯醇；紫草素；白血病；细胞分化；细胞凋亡

英文摘要： Previous prescriptions contained extracts from Zicao Lithospermum erythrorhizon Sieb. et Zucc in TCM had been proved their chemotherapeutic effects on leukemia, which were closely related to Blood cooling and Circulation invigorating in TCM. Originally, the drug-induced differentiation and apoptosis were seemed as two mechanisms differing in leukemia chemotherapy. However, currently, those two mechanisms were found related to intracellular redox homeostasis at various levels. Recently, our group and others' found the leukemia cells were sensitive to Shikonin among all tumor cell lines. The compound was further proved its stronger thoil-modified activities. For example, Shikonin could induced leukemia cell differentiation and apoptosis. The mechanism(s) involved into this cytotoxicities become an urgent theoretical problem. Thus current project aim to determine the role of cellular redox homeostasis and the involvement of thiols modification in association with Shikonin treatments in previous setup leukemia differentiation and/or apoptosis modes. Any breakthrough in the project will not only help to understand the reason of the Shikonin special cytotoxicity on leukemia cells, but also gives additional evidences and supports to The redox regulation theory.

英文关键词： Thiol;Shikonin;Leukemia;Cell differentiation;Cell apoptosis