组蛋白去乙酰化酶抑制剂辛二酰-双羟肟酸对乳腺癌细胞增殖的影响

Effect of suberoyl bishydroxamic acid on the proliferation of breast cancer cells

背景与目的:目前乳腺癌发病率仍居首位,是严重威胁女性健康的主要肿瘤之一。组蛋白去乙酰化酶抑制剂辛二酰双羟肟酸(suberic bishydroxamate,suberoyl bishydroxamic acid,SBHA)能够抑制组蛋白去乙酰化酶(histone deacetylase,HDAC)中的HDAC1和HDAC3的活性,选择性抑制某些肿瘤的生长而对正常细胞无不良反应。本实验旨在研究SBHA对人乳腺癌细胞增殖及周期的影响。方法:将不同浓度的SBHA以不同时间作用于乳腺癌MCF-7及MDA-MB-231细胞,用WST-8法检测其对细胞增殖能力的影响;用相差显微镜观察药物对细胞形态学变化;用流式细胞仪分析细胞周期。结果:SBHA呈时间和剂量依赖性抑制乳腺癌细胞增殖,使细胞形态发生明显变化,明显使G0～G1期细胞比例增高,S期细胞比例降低,与对照组比较差异有统计学意义(P>0.05)。结论:SBHA具有抑制人乳腺癌细胞增殖作用,使细胞阻滞在G0～G1期。

Background and purpose： The incidence of breast cancer ranks first in the female malignant tumor, and seriously threaten to women＇s health. The histone deacetylase inhibitor suberic bishydroxamate （SBHA） could inhibit the activity of HDAC1 and HDAC3. The growth of some tumor cells is selectively inhibited by SBHA without adverse effects on normal cells. In this study, we investigated the effects of SBHA on the proliferation and cell cycle of breast cancer cells. Methods： MCF-7 and MDA-MB-231 cells were exposed to different concentrations of SBHA for different periods of time. Cell viability was investigated in the breast cancer MCF-7 and MDA-MB-231 cells with SBHA alone at various concentrations and time points by WST-8. Cell cycle was analyzed by flow cytometry （FCM）. Light microscopy was used to observe morphological change. Results： Compared with the control group, the growth velocity was significantly slower in experimental group, and the changes presented concentration （P〈0.001） and time-dependence （P〈0.05）. Changes of cell morphology were found. G0-G1 phase arrest was been observed, and the percentage of cells in S phase decreased notably in the experimental group. Conclusion： SBHA could repress markedly the proliferation of MCF-7 and MDA-MB-231 cells, arrest the cell sycle at G0-G1 phase.