【摘要】 探讨二烯丙基二硫(DADS)诱导人胃癌MGC803细胞分化过程中组蛋白乙酰化状态的改变情况。运用形态学方法及成瘤实验观察DADS诱导MGC803细胞分化,应用Western印迹观察DADS诱导MGC803细胞分化与其调控细胞组蛋白乙酰化水平和相关p21WAF1的关系。形态学观察结果显示,30mg/LDADS处理MGC803细胞24h后,细胞异型性明显减少,且经裸鼠成瘤实验证实,处理后的细胞均未在裸鼠体内形成肿瘤;Western印迹显示,30mg/LDADS处理细胞12h后,其组蛋白H3乙酰化程度明显升高,与未处理组比较增加了38%(P<0.05);H4乙酰化程度无明显改变。用15、30、60mg/LDADS处理细胞12、24h后,p21WAF1均较对照组升高,以30mg/LDADS处理24h升高最显著。研究结果表明,DADS可诱导MGC803细胞分化,其作用可能与增加核组蛋白乙酰化水平及p21WAF1表达有关。更多还原

【Abstract】 We previously reported that diallyl disulfide (DADS) could significantly induce the differentiation in human gastric cancer MGC803 cells. In this study, we further investigated the change of histone acetylation level and the expression of p21WAF1 in the differentiation induced by DADS in MGC803 cells in vitro. Experiment were divided into six groups: untreated group, treated group with 5 mmol/L sodium butyrate, treated groups with 15, 30, 60 mg/L DADS and treated group with 5 mmol/L SB+30 mg/L DADS. After treated with 30 mg/L DADS for 24h in vitro, 0.2 ml including 1×107 MGC803 cells were implanted into subcutaneous side in BALB/C nude mice. Morpho- logical changes were examined under light microscopy. Expression of acetylated histone H3, H4 and p21WAF1 were detected by Western blot. The results showed that MGC803 cells after 24 h treated with 30 mg/L DADS were fusiform multiplication, volume shrink, enlarged cytoplasm, diminished nucleus, descend karyoplasmic ratio, karyotin thinningz, decreased nucleoli and atypia reduced. The formation of xenograft tumor was not found. The acetylation level of histone H3 in MGC803 cells was elevated after treated by 30 mg/L DADS for 12 h, and the effect was higher 38 % than untreated cells (P<0.05), and acetylation H4 did not changed. At the same time, the expression of p21WAF1 also was increaser after treated by 15, 30, 60 mg/L DADS, and treated by 30 mg/L DADS was higher 34.6% and 60.8% than untreated at 12 h and 24 h, respectively. It is suggested that the differentiation of MGC803 cells induced by DADS possibly involved in increase of histone acetylation and expression of p21WAF1.更多还原