岩白菜素衍生物D-23抗白血病作用及机制研究  

Anti-leukemia Activities and Mechanisms of Bergenin Derivative D-23

作　　者：王聪 朱晶晶 郑秀静 叶加[1] 叶新山[2] WANG Cong;ZHU Jing-jing;ZHENG Xiu-jing;YE Jia;YE Xin-shan(Department of Molecular and Cellular Pharmacology,School of Pharmaceutical Sciences;State Key Laboratory of Natural and Biomimetic Drugs and School of Pharmaceutical Sciences,Peking University,Beijing 100191,China)

机构地区：[1]北京大学药学院分子与细胞药理学系,北京100191 [2]北京大学天然药物及仿生药物国家重点实验室,北京100191

出　　处：《中国药学杂志》2018年第19期1638-1644,共7页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金项目资助(21738001;81870876)

摘　　要：目的探讨岩白菜素衍生物D-23抗白血病作用及机制。方法以CCK-8法评价岩白菜素衍生物D-23的抗白血病细胞增殖活性;以流式细胞术、免疫荧光技术研究化合物D-23对白血病细胞凋亡、自噬的诱导作用;用免疫印记法(Western blot)探究化合物D-23诱导白血病细胞凋亡、自噬的分子机制。结果岩白菜素衍生物D-23可抑制人慢性髓系白血病K562细胞和人T淋巴细胞白血病Jurkat细胞的生长,诱导K562,Jurkat细胞发生凋亡和自噬。D-23可降低细胞的线粒体膜电位,抑制Akt和Hsp70蛋白的表达,并激活caspase 3蛋白和caspase 9蛋白;同时抑制P-mTOR蛋白(Ser 2448和Ser 2481)。结论岩白菜素衍生物D-23具有体外抗人白血病细胞增殖的作用,其机制是诱导K562细胞和Jurkat细胞发生凋亡和自噬。促凋亡可能与降低线粒体膜电位,激活caspase凋亡通路相关,促自噬可能与抑制Akt/m TOR信号通路相关。OBJECTIVE To study the anti-leukemia activities and mechanisms of bergenin derivative D-23. METHODS CCK-8 method was applied to investigate anti-tumor activities of D-23. Flow cytometry and immunofluorescence assay were used to observe the effects of D-23 on the apoptosis and autophagy in K562 and Jurkat human leukemia cell lines. Western blot analy- sis was used to investigate the mechanisms that compound D-23 induced tumor cell apoptosis and autophagy. RESULTS Berge- nin derivative D-23 could significantly inhibit the proliferation of K562 and Jurkat cells by inducing cell apoptosis and autophagy. The mitochondrial membrane potential was decreased, protein kinase B（Akt） and heat shock protein 70 （Hsp70） were inhibited, and the expressions of apoptotic related proteins caspase 3 and easpase 9 were activated. In addition, mammalian target of rapam- yein （P-roTOR） （ Set 2448 and Set 2481 ） protein was inhibited. CONCLUSION Bergenin derivative D-23 shows obvious an- ti-leukemia activities by inducing cell apoptosis and autophagy. The apoptosis may he associated with the reduction of mitochon- drial membrane potential and activation of caspase pathway. The autophagy may be related to the inhibition of Akt/mTOR signa- ling pathway.

关 键 词：岩白菜素衍生物D-23 抗白血病 促凋亡 促自噬 

分 类 号：R965[医药卫生—药理学]