丹参酮类化合物对NB4细胞的增殖抑制与构效关系探讨  

Proliferation inhibition of tanshinones on NB4 cell line and its structure-activity relationship

作　　者：傅慧敏[1] 储婷[1] 李慧[2] 石华月[1] 张青[1] 张娜[1] 毛声俊[1] 

机构地区：[1]四川大学华西药学院,四川成都610041 [2]四川省医学科学院.四川省人民医院血液科,四川成都610072

出　　处：《华西药学杂志》2012年第3期253-256,共4页West China Journal of Pharmaceutical Sciences

基　　金：国家重大新药创制科技重大专项课题(2009ZX09310-002;2009ZX09503-020);高等学校博士点基金新教师资助项目(20070610050);四川省卫生厅项目(303.005.002.280.040)

摘　　要：目的比较丹参酮类化合物对人急性早幼粒细胞白血病NB4细胞的体外增殖抑制作用,并探讨其分子结构与细胞毒性之间的关系。方法采用改良MTT法测定不同浓度的丹参酮类化合物与细胞共培养一定时间后对NB4细胞的增殖抑制作用;采用倒置显微镜观察其细胞形态。结果供试丹参酮类化合物均能有效抑制NB4细胞的增殖,其抑制作用呈明显的时间和剂量依赖性。与NB4细胞共培养24 h后,二氢丹参酮Ⅰ与丹参酮Ⅰ的IC50值分别为1.86、3.62μg·mL-1,丹参酮ⅡA和隐丹参酮的IC50值均大于10μg·mL-1;共培养48 h后二氢丹参酮Ⅰ、丹参酮Ⅰ、丹参酮ⅡA、隐丹参酮的IC50值分别为0.65、1.41、1.83、5.41μg·mL-1;72 h后的IC50值分别为0.28、0.33、0.45、2.59μg·mL-1。结论 4种丹参酮类化合物对NB4细胞均具有增殖抑制作用,作用强度大小依次为二氢丹参酮Ⅰ、丹参酮Ⅰ、丹参酮ⅡA、隐丹参酮,提示丹参酮类化合物的A环为芳环时可增强细胞毒性,C环的呋喃环结构可能影响其细胞毒性。OBJECTIVE To investigate the proliferation inhibitory effect of tanshinones（Tan） on human acute promyelocytic leukemia NB4 cell line in vitro and the relationship between their molecule structures and cytotoxicity.METHODS The modified MTT assay was adopted to evaluate the inhibitory effect of tanshinones on NB4 cells at different concentrations and different times.Inverted phase contrast microscopy was employed to observe the cell morphology.RESULTS Tan could inhibit the proliferation of NB4 cells effectively,and their inhibitory effects were all in concentration-and time-dependent manners.After incubation with NB4 cells for 24 hours,the IC50 of dihydrotanshinoneⅠand TanⅠwere 1.86 and 3.62 μg·mL-1,respectively,and above 10 μg·mL-1 for Tan ⅡA and cryptotanshinone after incubation 48 hours the IC50 of dihydrotanshinoneⅠ,Tan Ⅰ,TanⅡA and cryptotanshinone were 0.65,1.41,1.83 and 5.41 μg·mL-1,respectively.The IC50 were 0.28,0.331,0.45,2.59 μg·mL-1 for 72 h incubation,respectively.CONCLUSION All of the four Tan had proliferation inhibitory effect on NB4 cell line,with inhibition ability as follows：dihydrotanshinoneⅠTanⅠTanⅡA cryptotanshinone subsequently.The result indicated that the chemical structure of aromatic ring A of tanshinones could enhance their cytotoxicity and the structure of furan ring C might influence the cytotoxicity.

关 键 词：丹参酮 NB4细胞 增殖抑制 构效关系 

分 类 号：R96[医药卫生—药理学]