DNA甲基转移酶抑制剂SGI-1027对人肝细胞癌细胞增殖及凋亡的影响

Effect of DNA Methyltransferase Inhibitor SGI-1027 on Proliferation and Apoptosis of Human Hepatocellular Carcinoma Cells

目的探讨SGI-1027对肝细胞癌细胞增殖及凋亡的影响。方法给予不同浓度(0、5、10、15、20、25、30和35μmol/L)的SGI-1027处理Huh7细胞24 h后,MTS法检测SGI-1027对Huh7细胞增殖活性的影响。实验组Huh7细胞中加入SGI-102730μmol/L,对照组Huh7细胞中仅加入等量0.1%DMSO;碘化丙啶染色和流式细胞仪检测SGI-1027对Huh7细胞周期的影响;Annexin V-FITC/PI双染法和流式细胞仪检测SGI-1027对Huh7细胞凋亡的影响;TUNEL染色观察SGI-1027处理后Huh7细胞形态变化。结果 SGI-1027在Huh7细胞中的IC_(50)为27.3μmol/L,SGI-1027能够抑制Huh7细胞增殖,并呈剂量依赖性。SGI-1027不影响Huh7细胞周期;SGI-1027能够诱导Huh7细胞凋亡,对照组和实验组的凋亡率分别为(3.242±0.204)%和(46.57±2.512)%(P<0.05)。TUNEL染色观察对照组细胞呈圆形,而实验组细胞呈典型凋亡表现,对照组和实验组凋亡细胞百分率分别为(1.077±0.407)%和(58.24±8.427)%(P<0.05)。结论 SGI-1027能够抑制Huh7细胞增殖,并且能够诱导其凋亡。

Objective To elucidate the inhibitory effect of SGI-1027 on cell proliferation and apoptosis of Huh7 cells. Methods Huh7 cells were treated with different concentrations （0,5,10,15,20,25,30, and 35μmol/L） of SGI-1027 for 24 h. MTS assay was performed to detect cell proliferation. Huh7 cells treated with 0.1% DMSO were used as the control group, and those treated with 30μmol/L SGI-1027 as the experimental group. Flow cytometry was performed to study the cell cycle, and Annexin V-FITC/PI detection for studying cell apoptosis. TUNEL staining was performed to observe changes in cell morphology. Results The resuhs of the MTS assay revealed that SGI-1027 significantly inhibited the proliferation of Huh7 cells in a dose-dependent manner, and the ICs0 was 27.3μol/L. SGI-1027 did not block the cell cycle of Hnh7 cells, but induced cell apoptosis in Huh7 cells. The rates of apeptosis were 3.242%±0.204% in the control group and 46.57%±2.512% in the experimental group （P 〈 0.05 ）. In the experimental group, typical apoptotic nucleus alterations were observed by fluorescence microscopy after TUNEL staining. The percentage of apoptotic cells was 1.077%±0.407% in the control group and 58.24%±8.427% in the experimental group （P 〈 0.05 ）. Condusion SGI-1027 inhibits Huh7 cell proliferation and induces apoptosis in vitro.