蓝莓花青素对HepG2细胞凋亡及组蛋白乙酰化修饰的影响

Effects of blueberry anthocyanin on apoptosis and histone acetylation in HepG2 cells

目的:探讨蓝莓花青素对人肝癌HepG2细胞凋亡及组蛋白乙酰化修饰的影响。方法:从贵州麻江蓝莓中提取花青素,用高效液相色谱法检测花青素的含量并鉴定。观察蓝莓花青素孵育后,HepG2细胞的形态变化、细胞增殖与凋亡情况,以及细胞组蛋白H3K9、H3K14、H3K18、H3K27乙酰化修饰的情况。结果:与无处理的对照组HepG2细胞比较,不同浓度蓝莓花青素(50、100、150、200、300μg/mL)处理HepG2细胞48 h后,HepG2细胞体积明显缩小,细胞增殖明显抑制(均P<0.05),凋亡明显增加,且作用呈随浓度增加而增强;不同浓度蓝莓花青素(50、100、200μg/mL)孵育48 h后,HepG2细胞组蛋白H3K9、H3K14、H3K18、H3K27乙酰化修饰明显增加(均P<0.05),且呈浓度依赖性。结论:蓝莓中花青素对HepG2有抑制增殖的作用,其机制可能通过增加组蛋白乙酰化修饰而促进细胞凋亡有关。

Objective： To investigate the effect of blueberry anthocyanin on apoptosis and histone acetylation modification in human hepatocellular carcinoma HepG2 cells. Methods： The anthocyanin was extracted from blueberries native to Majiang county of Guizhou province, and the content determination and identification of anthocyanin were performed by high performance liquid chromatography. In HepG2 cells after incubation with blueberry anthocyanin, the morphological changes, cell proliferation and apoptosis as well as the acetylation ofhistone H3K9, H3K14, H3K18, and H3K27 were observed.Results： Compared with untreated control HepG2 cells, in HepG2 cells after incubation with different concentrations of blueberry anthocyanin （50, 100, 150, 200, and 300 μg/mL） for 48 h, the cell volume was obviously reduced, proliferation was significantly inhibited （all P〈0.05） and apoptosis was remarkably increased, and all these effects were increased with increasing concentration of blueberry anthocyanin; the acetylation of histone H3K9, H3K14, H3K18 and H3K27 were significantly enhanced in HepG2 after treatment with different concentrations of blueberry anthocyanin （50, 100 and 200 μg/mL） for 48 h （all P〈0.05）, with a concentration- dependent manner. Conclusion： Blueberry anthocyanin has inhibitory effect on the proliferation of HepG2 cells, and the mechanism may probably be related to its enhancing histone acetylation and thereby promoting cell apoptosis.