2-甲氧基雌二醇诱导MUTZ-1细胞凋亡及对端粒酶活性的影响  

Alterations of telomerase activity and apoptosis induced by 2-methoxyestradioi in human myelodysplastic syndrome cell line MUTZ-1

作　　者：夏国华[1] 陈宝安[1] 芦慧霞[1] 丁家华[1] 邵泽叶[1] 高冲[1] 

机构地区：[1]东南大学临床医学院附属中大医院,南京210009

出　　处：《中华血液学杂志》2007年第3期199-202,共4页Chinese Journal of Hematology

基　　金：国家自然科学基金资助项目（00-R-318）.志谢：MUTZ-1细胞由德国乌尔姆大学医学院Dohner K和Dohner H惠赠.在此深表谢意

摘　　要：目的探讨2-甲氧基雌二醇（2-ME）诱导骨髓增生异常综合征（MDS）细胞株MUTZ-1细胞凋亡及其对细胞端粒酶活性表达的影响，以及细胞凋亡和端粒酶活性之间的相关性。方法采用不同浓度的2-ME处理MUTZ-1细胞，用流式细胞术检测细胞凋亡率和细胞周期的改变；用端粒重复序列扩增-酶联免疫吸附试验（TRAP-ELISA）检测细胞端粒酶活性变化。结果1、2和4μmol／L2-ME分别作用MUTZ-1细胞12h，流式细胞术检测出G0／G1期和S期细胞逐渐减少，G2／M期细胞明显增多（P〈0．05），细胞被阻滞于G2／M期；1和2μmol／L 2-ME作用MUTZ-1细胞12h，两组凋亡率均无明显增加（P〉0．05）；1、2和4μmol／L2-ME作用MUTZ-1细胞36h时，凋亡率为（12．87±0．86）％～（21．82±1．71）％，2-ME诱导细胞凋亡具有时间和剂量依赖性；2-ME诱导MUTZ-1细胞凋亡的同时伴随着端粒酶活性下调，且随着2-ME浓度增加和作用时间延长，端粒酶活性抑制作用增强；端粒酶活性下调与G2／M期细胞数呈负相关（r=-0．979，P=0．021），与细胞凋亡率呈负相关（r=-0．970，P=0．030）。结论2-ME诱导MUTZ-1细胞凋亡并抑制其端粒酶活性可能是其抗肿瘤的机制之一。Objective To study the effect of 2-methoxyestradiol（2-ME） on telomerase activity expression and apoptosis in human myelodysplastic syndrome cells line MUTZ-1. Methods MUTZ-1 cells were incubated with different concentrations of 2-ME, apoptosis rate and cell cycle were measured by flow cytometry （FCM）. Telomerase activity in MUTZ-1 cells was examined by telomeric repeat amplification protocol-Enzyme linked immunosorbent assay（TRAP-ELISA）. Results The FCM analysis showed that cells in G0/G1 phase and S phase were decreased, while in G2/M phase increased after exposed to 1,2 and 4 μmol/L of 2- ME for 12 hours（P〈0.05）. 1 and 2 μmol/L of 2-ME had no notable effect on MUTZ-1 cells as compared with the control group（P〉0.05）. Cells incubated with 1, 2 and 4 μmol/L of 2-ME for 36 hours were induced apoptosis, the percentage of apoptosis was between （ 12.87 ± 0.86） % and （ 21.82 ± 1.71 ） % with a dose- and time- dependent manner. Telomerase activity was significantly inhibited in these concentration and negatively correlated with cell number in G2/M phase（ r = -0. 979, P =0.021 ） and increased apoptosis（ r = -0. 970 ,P = 0.030 ）, respectively. Moreover, the inhibition effect of telomerase activity was enhanced in a dose- and time- dependent manner. Conclusions 2-ME-induced apoptosis and inhibition of telomerase activity provide a possible mechanism for explaining the 2-ME＇ s anticancer activity.

关 键 词：2-甲氧基雌二醇 端粒酶 细胞凋亡 细胞周期 骨髓增生异常综合征 MUTZ-1细胞 

分 类 号：R686[医药卫生—骨科学]