正常人肝细胞和肝癌细胞对力达霉素诱导的有丝分裂性细胞死亡的差异  

Difference of mitotic cell death induced by lidamycin in human hepatoma cells and normal liver cells

作　　者：杨啊晶[1] 梁越欣[1] 王真[1] 李电东[1] 何琪杨[1] 

机构地区：[1]北京协和医学院中国医学科学院医药生物技术研究所,北京100050

出　　处：《中国新药杂志》2009年第18期1777-1782,共6页Chinese Journal of New Drugs

基　　金：国家自然科学基金项目(30672482;30572204)

摘　　要：目的:探讨力达霉素(lidamycin,LDM)诱导人肝癌BEL-7402和正常人肝L-02细胞出现的有丝分裂性细胞死亡的差异。方法:采用MTT法观察LDM对BEL-7402和L-02细胞生长曲线的影响;使用Gi-emsa染色和流式细胞术观察有丝分裂性细胞死亡特征;用Western blot法检测蛋白表达变化。结果:LDM抑制BEL-7402和L-02细胞的生长,二者均表现出有丝分裂性细胞死亡的特征,即细胞体积增大、G2/M期阻滞、出现多核化,但BEL-7402细胞对LDM更敏感。在LDM处理的BEL-7402和L-02细胞中,与凋亡相关的Bax和Smac的蛋白表达水平没有增加,caspase-3和caspase-9未被活化,但L-02细胞的Akt通路被激活。结论:人正常L-02细胞对LDM引起的有丝分裂性细胞死亡明显低于人肝癌BEL-7402细胞,对LDM的反应敏感性存在差异的原因可能与Akt信号通路有关。Objective：To investigate the difference of mitotic cell death induced by lidamycin （LDM） in human hepatoma BEL-7402 cells and normal liver L-02 cells. Methods：Cell growth curve was determined by MTT assay. The LDM-induced mitotic cell death was observed by Giemsa staining and flow cytometry. The expression levels of protein were analyzed by Western blot. Results ： LDM inhibited the growth of BEL-7402 and L-02 cells, showing the characteristics of mitotic cell death, including enlargement of cell volume, appearance of muhinucleation, arresting in G2/M phase of cell cycle. BEL-7402 cells were more sensitive to LDM than L-02 cells. In LDM-treated BEL-7402 and L-02 cells, the protein levels of Bax and Smac were not increased, caspase-3 and caspase-9 were not activated yet. But Akt pathway was activated by LDM in L-02 cells. Conclusion：The rate of mitotic cell death induced by LDM in L02 cells is lower than that of BEL-7402 cells. The different sensitivities responding to LDM might be associated with Akt pathway.

关 键 词：力达霉素 有丝分裂性细胞死亡 细胞凋亡 人肝细胞 人肝癌细胞 

分 类 号：R978.1[医药卫生—药品]