雷公藤甲素对MV4-11细胞增殖的影响及RAS／ERK／MAPK通路相关机制研究  

Effect of proliferation of triptolide on MV4-11 cells and its mechanism research associated with RAS/ERK/MAPK

作　　者：刘朵平[1] 马梁明[1] 鹿育晋[1] 王涛[1] 郑凤丽[1] 阎玮兰 Liu Duoping Ma Liangming Lu Yujin Wang Tao Zheng Fengli Yan Weilan(Department of Hematology, Dayi Hospital Affiliated to Shanxi Medical University, Taiyuan 030032, Chin)

机构地区：[1]山西医科大学附属大医院血液科,太原030032

出　　处：《中国医师杂志》2017年第6期844-847,共4页Journal of Chinese Physician

基　　金：山西省自然科学基金（2015011094）;山西省科技成果转化引导专项（201604D131005）

摘　　要：目的探讨雷公藤甲素（TP）对Fms样酪氨酸激酶3基因内部串联重复（FLT3一ITD）突变阳性急性髓系白血病细胞株MV4—11的增殖、凋亡影响及RAS／细胞外信号调节激酶／丝裂原活化蛋白激酶（ERK／MAPK）通路相关机制。方法用不同浓度的TP分别处理MV4—11细胞，在不同的时间点，采用四甲基偶氮唑蓝法测定增殖抑制率，流式细胞术测定凋亡率，实时荧光定量PCR法测定FLT3、RAS、ERK、叉头框蛋白M1（FOXM1）、c—Myc的mRNA表达水平。结果TP处理MV4—11细胞后，其增殖抑制率明显增高，且呈剂量一时间依赖性；10、20nmol／L的TP分别处理MV4-11细胞，48h的凋亡率分别为（17．30±0．56）％、（35．77±0．55）％，72h的凋亡率分别为（49．83±0．45）％、（68．90±0．75）％；PCR显示FLT3mRNA的表达明显下降，RAS、ERK、FOXM1、c—Myc的mRNA的表达均降低。结论TP能明显抑制MV4—11细胞的增殖并诱导细胞凋亡，其作用机制是通过抑制RAs／ERK／MAPK通路相关基因的表达发挥作用。Objective To explore the effect of proliferation and apoptosis, and research its mecha- nism associated with RAS/extracellular signal regulated kinasc/mitogen-activated protein kinase （RAS/ ERK/MAPK） in Fms-like tyrosine kinase 3-internal tandem duplication （FLT3-1TD） mutation acute lym-phocytic leukemia cell line MV4-11 cells treated by triptolide （TP）. Methods MV4-11 cells were respec-tively treated by triptolide with diverse concentrations and different times. The proliferation inhibition rate was measured by methyl thiazolyl tetrazolium, the apoptosis rate was detected by flow cytometry,the mRNA expressions of FLT3, RAS, ERK, forkhead box protein M1 （ FOXM1 ） , and c-Myc were analyzed by real- time fluorescent quantitative polymerase chain reaction （PCR）. Results The proliferation inhibition rate markedly increased in a dose-time dependent manner after MV4-11 cells were treated by TP. After cells were treated with 10, and 20 nmoL/L TP, respectively, the apoptosis rates at 48 h were （ 17.30±0. 56）% , （35.77±0. 55）%, and those at 72 h were （49. 83±0. 45）%, （68.90±0. 75）% correspondingly. PCR data showed that the mRNA level of FLT3 mRNA decreased obviously, and that of RAS, ERK, FOXM1, and c-Myc also decreased. Conclusions Triptolide could significantly inhibit the MV4-11 cells prolifera- tion and induce cell apoptosis, and its mechanism might be through inhibiting the expression of related genes on RAS/ERK/MAPK signaling pathway.

关 键 词：雷公藤内酯/药理学 白血病 髓样 急性/药物疗法 细胞增殖/药物作用 基因 ras 细胞外信号调节MAP激酶类 丝裂原激活蛋白激酶激酶类 

分 类 号：R285[医药卫生—中药学]