新型氨基甾体诱导白血病细胞分化机理的研究

It was found in this project that the novel aminosteroids possessed biological activities not only in proliferation inhibition but also in differatiation and apoptosis induction both in human and murine leukemia cells. These compounds can induce differatiation of myeloid leukemia cells toward macrophage-like cells and erythroid leukemia cells toward erythroid-like and megakaryocyte-like cells. They can treat leukemia suffered by mouse. It was also found that they can increase calcium ion concentration and decrease hydrogen ion concentration in leukemia cells. Meanwhile, c-myc gene was down-regulated and both mafB and egr-1 genes were up-regulated by these compounds in leukemia cells. These kinds of compounds were metabolized in the original form in leukemia cells. The related research results have been published in two papers in the well-known journal Leukemia Research. There are eight papers already published in national academic key journals. The research results were reported in two separate international meetings and drew attetion of all participants. There are another three papers now in submitting or preparing. It was proved that the novel aminosteroids possessed denovo new action mechanisms and can be developed as new pharmacological tool-drugs or novel differatiation inducing agents in leukemia treatment.. .

新型氨基甾体系本人在国际上首次合成并被CA确定为全新化合物。研究其对粒系及红系白血病细胞系诱导分化的药效学，用质谱仪研究其活性代谢产物，用荧光分光光度计研究钙和氢离子在传导信息中的作用，用流式细胞仪研究粒单系分化基因MafB及红系分化基因Ets－1在其诱导分化中的表达。从而为开发新型诱导分化剂及过度到临床应用提供坚实的理论基础。