摘要
目的:探讨抑制前列腺素E2合酶1(mPGES-1)表达对人急性白血病K562细胞在裸鼠体内成瘤的影响及其可能的机制。方法:通过shRNA干扰技术下调K562细胞中mPGES-1表达,实验设立了如下研究小组:①干扰组(KD),②阴性细胞(NC)非特异序列shRNA干扰组;③未处理组(CON组);应用Western blot法检测β-catenin和cyclin D1在3组细胞中的表达;构建K562细胞人-裸鼠移植瘤模型,观察移植瘤的生长情况;应用HE染色观察各组肿瘤组织的结构;应用免疫组织化学法检测β-catenin和cyclin D1的表达水平。结果:与CON组和NC组比较,细胞体外实验结果显示KD组β-catenin和cyclin D1表达量减少(P<0.05);动物体内实验结果显示,KD组瘤体生长明显减慢,移植瘤体积明显缩小,重量明显减轻(P<0.01);HE染色显示,KD组细胞排列相对松散,间质较多,肿瘤细胞核小,细胞质较少;免疫组织化学检测显示,KD组β-catenin和cyclin D1表达量明显下降(P<0.05)。结论:下调mPGES-1表达能显著抑制人急性白血病K562细胞在裸鼠体内成瘤,其机制可能与抑制β-catenin和cyclinD1表达相关。
Objective：To investigate the effects of shRNA targeting mPGES-1 on tumorigenicity of human acute leukemia K562 cells in nude mice in vivo and its mechanisms.Methods：For experiment 3 groups including KD group（expression of mPGES-1 in K562 cells was down-regulated by shRNA）,CON（cells without any treatment） and NC group（cells treated with nonspecific-sequence shRNA） were set-up.Western blot was used to test the expression of（3-catenin and cyclinDl in cells.Then the cells of 3 groups were implanted into BALB/c nude mice subcutaneously to establish murine xenograft model.The growth state of the mice and the size of the xenograft tumor were recorded.HE staining was used to observe the morphology of xenograft tumor.Expressions of p-catenin and cyclinDl in xenograft tumor were detected by immunohistochemical staining.Results：Jn vitro the expression of p-catenin and cyclinDl in KD group were lower than the CON group and NC group（P〈 0.05）.In vivo the tumor volume and weight of KD group were significant smaller than the other two groups（P 〈0.01）.HE staining showed that tissues in the KD group were relatively looser in arrangement with smaller cell nucleus and less cytoplasm.The expression of p-catenin and cyclinDl in the KD group were remarkable weak as compared with that in CON group and NC group（P〈 0.05）.Conclusion：Down-regulating the expression of mPGES-1 by shRNA may significantly inhibit the tumorigenicity of K562 cells in nude mice in vivo and its mechanism may be related with the inhibition of expression of p-catenin and cyclinDl.
出处
《中国实验血液学杂志》
CAS
CSCD
北大核心
2017年第1期55-60,共6页
Journal of Experimental Hematology
基金
2012年国家自然青年科学基金(81200342)
2012年广东省医学科学技术研究基金(A2012182)
2014年度广东省公益研究与能力建设专项基金项目(2014A020212085)
作者简介
通讯作者：李益清，副教授．E-mail：sumliyiqing@163．com
