【作者】 向姝霖； 肖晓岚； 苏琦； 赵洁； 黄琛； 解娜； 周秀田； 董琳；

【Author】 Xiang Shu-Lin Lin Hui Su Qi Xiao Xiao-Lan Huang Chen XieNa Zhou Xiu-Tian Dong Lin Cancer Research Institute, Nanhua University, Hengyang, Hunan Province 421001, China

【机构】 南华大学肿瘤研究所；

【摘要】 目的:探讨二烯丙基二硫(diallyl disulfide,DADS) 诱导人胃癌MGC803细胞分化过程中组蛋白乙酰化状态及其调控p21WAF1蛋白表达改变的情况。方法:运用形态学方法、裸鼠成瘤实验及Western blot观察DADS体外诱导 MGC803细胞分化的作用机制与其调控细胞组蛋白乙酰化水平和p21WAF1蛋白的关系。结果:DADS处理MGC803细胞后,细胞散在分布生长,胞质更丰富,细胞核变小,染色变淡,核仁数量明显减少,核浆比例下降,异型性明显降低。裸鼠成瘤实验证实,经DADS处理后的MGC803细胞移植裸鼠体内均未形成肿瘤。Western blot结果表明,30mg／L、60mg／ LDADS处理MGC803细胞6h后,组蛋白H3乙酰化程度明显升高,12h时达高峰,较对照组增加38％,呈药物浓度依赖, 12 h时,30mg／L DADS的效果与5 mol／L丁酸钠相同,为对照组的1．38倍, 而30mg／L DADS与5 mol／L 丁酸钠共同处理时,H3乙酰化程度与两者单独处理时升高 18％,H4乙酰化程度改变不明显,仅在60 mg／L DADS处理12h时有增加,但在两药合用时,DADS可增强丁酸钠H4 的作用,其程度比单用丁酸钠时增加了5％。H4乙酰化程度无明显改变。p21WAF1蛋白增加出现在DADS处理12 h后, 24 h达到最高。结论:DADS诱导MGC803细胞分化的作用可能是通过增加其核组蛋白乙酰化水平及p21WAF1蛋白表达完成的。更多还原

【Abstract】 Objective: To investigate the change of hi-stone acetylation level in the differentiation induced by diallyl disulfide (DADS) in human gastric cancer MGC803 cells. Methods: Morphologic observation, bearing tumor experiment and Western Blot which measured the histone acetylation and related protein p21WAF1 were used to elucidate the possible mechanism of DADS-induced MGC803 cells differentiation in vitro. Results: morphologic observation indicated morphology changed and atypia significantly decreased when treated with DADS in MGC803 cells. The experiment of bearing tumor on Blab/C nude mice proved the formation of xenograft tumor declines obviously after MGC803 cells were treated with DADS in vitro. By western blot, the acetylation level of histone H3 was elevated after treated by DADS at 6h, and the maximum effect was higher 38 % than untreated cells at 24h., at the same time, the expression of p21WAF1 also increased, but the acetylation level of histone H4 did not changed in MGC803 cells. Conclusion: DADS-induced differentiation of gastric cancer MGC803 cells possibly involved in the increase of histone acetylation and the expression of p21WAF1.更多还原