基于蛋白质相互作用网络与有效成分分子对接探索大黄虫丸治疗CML的机制  

Mechanism of Dahuang Zhechong Pill in treating chronic myeloid leukemia based on protein interaction network and the effective component

作　　者：滕文静[1] 孙长岗[2] 

机构地区：[1]上海中医药大学附属上海市中医医院,上海200071 [2]潍坊市中医院,潍坊261041

出　　处：《中华中医药杂志》2016年第5期1629-1637,共9页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金面上项目(No.81273987)~~

摘　　要：目的:本研究通过建立慢性粒细胞白血病(CML)遗传相关基因的蛋白质相互作用网络及体外细胞实验验证两部分,探索经典方剂大黄虫丸治疗慢性粒细胞白血病的内在机制及生物学行为。方法:筛选在线人类孟德尔遗传数据库中的CML遗传相关基因,应用Cytoscape 3.0软件和插件Agilent Literature Search 2.8,进行文本挖掘并建立CML的蛋白质相互作用网络;应用插件Clusterviz,发现网络中的可能包含的分子复合物;基于DAVID,富集分子复合物的生物学通路。针对关键通路JAK2-STAT5,采用MTT法、流式细胞术、Western Blot法进行体外细胞实验,观察大黄虫丸对K562细胞增殖及JAK2、STAT5表达的影响。结果:CML是一个受多种信号通路、多种基因构成的网络体系协同调控的复杂过程,并非简单地由某个基因或某条信号通路控制;而在该信号网络中,JAK2-STAT5很可能是"关键调控点",大黄虫丸能够抑制K562细胞的增殖,其内在作用机制可能与其影响JAK2-STAT5的表达有关。结论:CML蛋白质基因网络复杂,其中JAK2-STAT5很可能是关键节点,而大黄虫丸对K562细胞增殖的抑制作用机制之一是降低JAK2-STAT5通路的表达。Objective： Base on a prior clinical observation, the mechanism underlying the Dahuang Zhechong Pill in treating the chronic myeloid leukemia（CML） was explored through establishing related protein interaction networks and cell experiment, which will provide a theoretical and experimental reference for TCM in the treatment of blood system diseases. Methods： Chronic myelogenous leukaemia genetic genes involved in protein interaction network was established by searching the online Mendelian Inheritance in Man database（OMIM）, then the protein interaction network was formed by the application of Cytoscape software and plug-ins Agilent Literature Search. The molecular complexes in the protein interaction network were captured with plug-in Clusterviz. The biological pathways gathering molecular complexes were set up with DAVID. The effects of Dahuang Zhechong Pill on the proliferation of K562 cell and the expression of JAK2 and STAT5 were respectively detected by MTT, flow cytometry and Weston blot. Results： CML was cooperatively controlled by a complicated network consisted of many signal pathways and genes rather than single gene or particular signal pathway. And, JAK2-STAT5 pathway played a vital role in the network. Additionally, the mechanism underlying the inhibitory effects of Dahuang Zhechong Pill on the proliferation of K562 cells may relate to JAK2-STAT5 pathway. Conclusion： Chronic myeloid leukemia could be cooperatively controlled by complicated protein and gene network. JAK2-STAT5 pathway played a vital role in the network. Additionally, the mechanism underlying the inhibitory effects of Dahuang Zhechong Pill on the proliferation of K562 cells may relate to the down-regulation of JAK2-STAT5 pathway.

关 键 词：大黄虫丸 分子对接 蛋白质相互作用网络 慢性粒细胞白血病 JAK2-STAT5通路 

分 类 号：R285[医药卫生—中药学]