Zhao Hui-Hui, Chen Bao-An, Gao Chong, Shao Ze-Ye, Xia Guo-Hua, Ding Jia-Hua, Sun Yun-Yu, Wang Jun, Cheng Jian, Zhao Gang, Dohner K, Dohner H
Department of Hematology, Zhongda Hospital, Southeast University, Nanjing 210009, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2007 Aug;15(4):743-7.
To study the effects of sodium valproate (VPA) on human myelodysplastic syndrome cell line MUTZ-1. The cell proliferation was determined by MTT assay, apoptotic morphological features were observed by light microscopy and transmission electronmicroscopy, cell apoptosis and cell cycle shift were analyzed by flow cytometry (FCM). The results showed that VPA could inhibit the growth of MUTZ-1 cells in dose-and time-dependent manners. The typical apoptotic morphological features appeared in MUTZ-1 cells treated with 4 mmol/L VPA for 72 hours. Pyknosis of cells and nuclei, disintegration of nuclear chromatin and apoptotic body could be observed by light microscopy. Aggregation and margination of nuclear chromatin, concentration of plasm, increment of density and chromatin mass of irregular size could be observed by transmission electronmicroscope. The flow cytometric analysis indicated that the VPA could induce cell apoptosis, apoptosis rate increased in dose-dependent manner, ratio of cells at G(0)/G(1) phase increased and ratio of cells at S phase decreased in dose-dependent manner, the cells were arrested at G(0)/G(1) phase. It is concluded that the VPA can induce apotosis and inhibite proliferation of MUTZ-1 cells via arresting cells at G(0)/G(1) phase.
研究丙戊酸钠（VPA）对人骨髓增生异常综合征细胞系MUTZ-1的作用。采用MTT法检测细胞增殖，通过光学显微镜和透射电子显微镜观察细胞凋亡的形态学特征，运用流式细胞术（FCM）分析细胞凋亡及细胞周期变化。结果显示，VPA能以剂量和时间依赖性方式抑制MUTZ-1细胞的生长。用4 mmol/L VPA处理72小时后的MUTZ-1细胞出现典型的凋亡形态学特征。光学显微镜下可观察到细胞及细胞核固缩、核染色质解体和凋亡小体。透射电子显微镜下可见核染色质聚集和边缘化、细胞质浓缩、密度增加以及大小不规则的染色质团块增多。流式细胞术分析表明，VPA可诱导细胞凋亡，凋亡率呈剂量依赖性增加，G(0)/G(1)期细胞比例呈剂量依赖性增加，S期细胞比例呈剂量依赖性降低，细胞阻滞于G(0)/G(1)期。结论是，VPA可通过使细胞阻滞于G(0)/G(1)期诱导MUTZ-1细胞凋亡并抑制其增殖。
