二氢丹参酮Ⅰ对白血病THP1细胞的增殖抑制作用及其机制探讨  

Inhibitory effect of dihydrotanshinone Ⅰon the proliferation of leukemia THP1 cells and its action mechanism

作　　者：李慧[1] 何莹[2] 王慧洁[3] 向洪[2] 王春森[1] LI Hui;HE Ying;WANG Hui-jie;XIANG Hong;WANG Chun-sen(Department of Hematology,Sichuan Academy of Medical Sciences,Sichuan Provincial People Hospital Chengdu,Chengdu,610072,China;North Sichuan Medical College,Nanchong,637000,China;Key Laboratory of Drug Targeting and Drug Delivery System,School of Pharmacy,Ministry of Education,West China,Sichuan University,Chengdu 610041,China)

机构地区：[1]四川省医学科学院·四川省人民医院血液科,四川成都610072 [2]川北医学院,四川南充637000 [3]四川大学华西药学院&靶向药物及释药系统教育部重点实验室,四川成都610041

出　　处：《实用医院临床杂志》2018年第2期19-22,共4页Practical Journal of Clinical Medicine

基　　金：四川省科技厅科研基金资助项目(编号:2014JY0100)

摘　　要：目的探讨二氢丹参酮I对白血病THP1细胞的增殖抑制作用,并探讨其作用机制。方法将不同浓度的二氢丹参酮Ⅰ与THP1细胞共孵24、48及72 h,分别采用CCK8法、Annexin V/PI双染法检测其对THP1细胞的增殖抑制与促凋亡作用;采用Western blot法检测NF-κB、MAPK及PI3K细胞信号通路的蛋白表达。结果二氢丹参酮I与THP1细胞共孵24、48及72 h,其IC50值分别为6.2、4.3及4.1μmol/L。浓度为5μmol/L的二氢丹参酮Ⅰ与THP1细胞共孵24 h后,G0/G1期细胞比率均显著增加(P<0.01)。二氢丹参酮Ⅰ可使NF-κB、PI3K信号通路的蛋白表达下调,对MAPK信号通路的蛋白表达无显著影响。结论二氢丹参酮Ⅰ对THP1细胞具有增殖抑制作用并呈浓度及时间依赖性,其通过阻滞THP1细胞周期而促凋亡;其发挥抗肿瘤作用的机制可能与抑制NF-κB、PI3K细胞信号通路的蛋白表达有关。To investigate the inhibition effect of dihydrotanshinoneI(DTA I)on the proliferation of leukemia THP1 cells and explore its action mechanism.The THP1 cells were treated with various concentrations of DTA I for 24 h,48 h and 72 h,respectively.After treatment,the proliferation of the THP1 cells was determined by CCK8 assays.Flow cytometry was performed to examine the cell cycle and apoptosis of THP1 cells treated with 5μmol/L of DTA I labeled with Annexin PI for 24 h.Western blot was used to detect the expression of the NF-kappa B,MAPK and PI3K.DTA I showed inhibitory effect on the proliferation of THP1 cells.The calculated IC50 of DTA I for THP1 cells was 6.2μmol/L,4.3μmol/L and 4.1μmol/L at 24 h,48 h and 72 h,respectively.After treated with 5μmol/L of DTA I for 24 h,the percentage of apoptosis cells in the DTA I group was significantly higher than that in the control group(P<0.01).Compared with the control group,the proportion of cells in G 0/G 1 phase was increased(P<0.01)and those in S phase and G 2/M phase were decreased(P<0.05).DTA I significantly inhibited the expression of NF-κB and PI3K,but did not affect the expression of MAPK.We have confirmed that DTA I could inhibit the proliferation of THP1 cells,block the cell cycle,induce its apoptosis in dose and time dependent manner.The anticancer mechanisms of DTA I may be related to down-regulation of the expression of NF-κB and PI3K.

关 键 词：丹参酮Ⅰ 白血病 抑制作用 凋亡 信号通路 

分 类 号：R733.7[医药卫生—肿瘤]