Xia Guo-Hua, Chen Bao-An, Shao Ze-Ye, Lu Hui-Xia, Konstanze Döhner, Hartmut Döhner
Department of Hematology, The Affiliated Zhongda Hospital, Clinical Medical College of Southeast University, Nanjing 210009, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2007 Apr;15(2):296-301.
The study was aimed to investigate the mechanism of proliferation inhibition and apoptosis of MDS-RAEB MUTZ-1 cells induced by 2-methoxyestradiol (2-ME), the cell proliferation was determined by MTT assay, apoptosis rate was determined with annexinV-FITC/PI double staining and cell cycle was analyzed by flow cytometry (FCM) after MUTZ-1 cells were treated with different concentrations of 2-ME; the changes of morphologic features of MUTZ-1 cells were observed with Wright-Giemsa's staining; lactate dehydrogenase was determined by Beckman Counter; and agarose gel electrophoresis was used to verify whether 2-ME can induce apoptosis of MUTZ-1 cells. The results showed that 2-ME inhibited the proliferation of MUTZ-1 cells in a dose-and time-dependent manner and caused a sustained arrest at G(2)/M phase in MUTZ-1 cells; the typical apoptotic morphological features appeared in MUTZ-1 cells; the production of lactate dehydrogenase was up-regulated and the marked DNA ladder pattern of internucleosomal fragmentation was observed. It is concluded that the mechanism of proliferation inhibition and apoptosis of MUTZ-1 cells induced by 2-ME is probably related with the G(2)/M cell cycle arrest; 2-ME may be a potentially adjunctive anticancer drug useful to treat myelodysplastic syndrome.
本研究旨在探讨2-甲氧基雌二醇（2-ME）诱导骨髓增生异常综合征难治性贫血伴原始细胞增多（MDS-RAEB）MUTZ-1细胞增殖抑制及凋亡的机制，采用MTT法检测细胞增殖，用annexinV-FITC/PI双染法测定凋亡率，用流式细胞术（FCM）分析MUTZ-1细胞经不同浓度2-ME处理后的细胞周期；用瑞氏-吉姆萨染色观察MUTZ-1细胞形态学特征的变化；用贝克曼计数器测定乳酸脱氢酶；用琼脂糖凝胶电泳验证2-ME是否能诱导MUTZ-1细胞凋亡。结果显示，2-ME以剂量和时间依赖性方式抑制MUTZ-1细胞增殖，并使MUTZ-1细胞在G(2)/M期持续阻滞；MUTZ-1细胞出现典型的凋亡形态学特征；乳酸脱氢酶的产生上调，并观察到明显的核小体间断裂的DNA梯带模式。结论是，2-ME诱导MUTZ-1细胞增殖抑制及凋亡的机制可能与G(2)/M细胞周期阻滞有关；2-ME可能是一种潜在的辅助抗癌药物，对治疗骨髓增生异常综合征有用。
