青蒿琥酯和青蒿素抗肿瘤作用及其机制的初步研究  

Analyzing the mechanisms related with anti-cancer of artesunate and artemisinin

作　　者：陈立军[1] 姚丽[1] 靳秋月[1] 谢红[1] 呼文亮[2] 

机构地区：[1]中国人民武装警察部队医学院生化教研室,天津300162 [2]中国人民武装警察部队医学院,天津300162

出　　处：《现代生物医学进展》2009年第8期1428-1431,共4页Progress in Modern Biomedicine

基　　金：天津市科委课题资助项目(05YFJMJC08200)

摘　　要：目的:探讨人白血病细胞株K562经青蒿琥酯和青蒿素处理后基因表达的变化及其可能机制。方法:K562细胞经不同浓度青蒿琥酯和青蒿素处理24h后,倒置相差显微镜和荧光显微镜下观察细胞形态学变化,流式细胞仪检测细胞周期变化;提取细胞总RNA,将逆转录生成的cDNA与基因芯片杂交,分析杂交结果。结果:倒置光显微镜:细胞出现不同程度的皱缩,核分裂相减少,细胞密度下降,漂浮细胞增多。荧光显微镜:染色质高度浓缩、边缘化,凝聚成明亮的团块,即凋亡小体。流式细胞仪:G2期细胞的比例明显增加。芯片杂交分析数据,青蒿琥酯处理组有10条基因表达有差异,表达上调的基因有:p21、chk1,表达下调的基因有:cyclinB1、cyclinE1、E2F1、DNA-PK、hTERT、bcl-2、jnk、VEGF;青蒿素处理组有10条基因表达下调:cyclinD1、cdk4、cdk2、cdc2、DNA-PK、DNA-TopoI、mcl-1、erk、jnk、VEGF。结论:青蒿琥酯和青蒿素可以抑制K562细胞增殖,作用机制与改变细胞周期某些调控物质的基因表达、诱导K562细胞凋亡等有关。Objective： In order to understand how artesunate and artemisinin inhibited leukaemia cell line K562,on the molecular level,the gene chip was used to detect the expression panel of genes of leukaemia cell line K562 treated by artesunate. Methods： K562 cells were treated with artesunate and artemisinin for 24h,and then the cell morphology changes were studied under inverted light microscope.The cell cycle states were examined by flow cytometry analysis.Total RNA samples were obtained by TRIzol and were reversely transcribed to the cDNA.cDNA samples were hybridized to the gene chips.Hybridization signals were collected and analyzed by Gene Pix 4100A. Results： The numbers of drift cells were increased and the density of cells was decreased observing under inverted light microscope after K562 cells were treated artesunate and artemisinin for 24h. Morphology changes of cell apoptosis such as karyopyknosis and conglomeration were observed by Hoechst33342/PI staining.Flow cytometric analysis showed that cells were arrested in G2 phase. Hybridization analysis showed up-regulation of p21 and chkl, down-regulation of cyclinB 1, cyclinE 1, E2F1, DNA-PK, hTERT, bcl-2, JNK and VEGF in the artesunate -treated K562 cells; and down-regulation of CyclinD1, Cdk4, Cdk2, Cdc2, DNA-PK, DNA-TopoI, MCL-1, ERK, JNK and VEGF in the artemisinin-treated. Conclusion： Artesunate and artemisinin can inhibit the proliferation of leukaemia cell line K562. The mechanism is related to altering the expression of these genes involved in cell cycle and inducing apoptosis.

关 键 词：基因芯片 青蒿琥酯 青蒿素 细胞周期 细胞凋亡 

分 类 号：R730.5[医药卫生—肿瘤]