DADS体内诱导人胃癌细胞分化作用中组蛋白乙酰化的变化  

Role of histone acetylation in the differentiation of human gastric cancer cell induced by DADS in vivo

作　　者：向姝霖[1] 肖晓岚[1] 苏琦[1] 赵洁[1] 黄琛[1] 解娜[1] 周秀田[1] 周建国[1] 

机构地区：[1]南华大学肿瘤研究所,湖南衡阳421001

出　　处：《中国药理学通报》2006年第1期55-59,共5页Chinese Pharmacological Bulletin

基　　金：湖南省科研计划重大专项资助项目(No04SK1004);湖南省教育厅科研基金重点资助项目(No04A047)

摘　　要：目的观察二烯丙基二硫(DADS)在体内诱导胃癌细胞分化的作用及对人胃癌细胞移植瘤组蛋白乙酰化的影响。方法裸鼠皮下注入人胃癌细胞MGC803建立人胃癌异种移植模型,采用光学显微镜观察移植瘤细胞形态变化,流式细胞光度术和W estern b lot分析DADS对MGC803细胞移植瘤细胞周期分布的影响及瘤组织中p21WAF1蛋白、组蛋白H3、H4乙酰化的表达情况。结果腹腔注射DADS剂量为100、200 mg.kg-1时对移植瘤有明显生长抑制作用;光学显微镜显示经DADS处理后瘤细胞密度及异型性明显减小。流式细胞仪分析结果显示DADS呈浓度依赖性将移植瘤细胞阻滞在G2/M期。DADS浓度为100 mg.kg-1和200 mg.kg-1作用瘤细胞后,与对照组相比分别可使G2/M期细胞增加2.22和3.37倍。W estern b lot分析表明在G2/M期阻滞同时有组蛋白H3乙酰化表达增加,但组蛋白H4乙酰化表达水平不受DADS作用的影响;瘤组织中的p21WAF1蛋白表达量也随DADS浓度升高而上升。结论DADS对胃癌细胞裸鼠移植瘤的生长有明显抑制和诱导分化作用,这种抑制可能与其阻滞移植瘤细胞周期、上调瘤细胞组蛋白乙酰化及p21WAF1蛋白水平有关。Aim To observe effect of DADS on the differentiation of gastric adenocarcinoma cells and acetylation of human gastric cancer tumor cell transplantable histone. Methods Human gastric adenocarcinoma heterotransplantable tumor model was constructed through subcutaneously injecting MGC803 cells to nude mice. Morphologic changes of xenograft tumor cells were observed with optical microscope, the influence of DADS on xenograft tumor cells generationcycle distribution,the expression of p21^WAF1 protein, histone H3 and and H4 acetylion were analyzed with flow cytometry and Western blot. Results There was obvious growth inhibitory effect of xenograft tumor while abdominal injection dose were 100 and 200 mg·kg^-1 DADS; cells density and heteromorphism decreased after treated with DADS. Flow cytometry analysis revealed that treating xenograft tumor cells with increasing quantities of DADS increased the percentage of cells in the G2/M phase. The proportion of xenograft tumor cells in the G2/M phase after treatment with 100 mg · kg^-1 and 200 mg· kg^-1 DADS was 2.22 and 3.37 times of that in NS group. Western blot analysis showed H3 acetylion increase along with G2/M arrest of xenograft tumor cells by DADS. DADS didn＇t influence the expression level of H4 acetylion ; the expression of p21 WAFI protein in xenograft tumor increased along with the increases in the concentration of DADS. Conclusion DADS cansignificantly inhibit the growth of human gastric carcinoma xenograft in BALB/C nucle mice and induce cell differentiation, which might be related with up-regulation of histone a cetylization and p21^WAF1 protein level.

关 键 词：二烯丙基二硫 胃肿瘤 BALB/C裸鼠 组蛋白乙酰化 细胞周期 P21^WAF1蛋白 

分 类 号：R282.71[医药卫生—中药学] R284.1[医药卫生—中医学]