姜黄素下调结直肠癌细胞Notch1信号通路研究  

Study of Curcumin on Down-regulating Notch1 Pathway in Colorectal Cancer Cells

作　　者：杨芳[1] 刘少琼[1] 李春花[1] 尹玲[1] 刘娅[1] 谢婉莹[1] 

机构地区：[1]南华大学附属第一医院,湖南衡阳421001

出　　处：《湖南中医药大学学报》2015年第4期10-13,50,F0003,共6页Journal of Hunan University of Chinese Medicine

基　　金：湖南省自然科学基金项目(11JJ6083)

摘　　要：目的检测Notch1信号通路中Notch intracellular domain蛋白(NICD1蛋白)在大肠腺癌组织中表达的情况;探讨姜黄素对人结肠癌细胞SW480及HT29细胞中Notch1信号通路的影响。方法二步法免疫组化检测40例结直肠癌、31例癌旁肠组织石蜡切片中Notch1 intracellular domain蛋白(NICD1)的表达情况,通过对比人结肠直肠癌与癌旁正常肠黏膜细胞中蛋白阳性表达率判断NICD1蛋白与人结直肠癌的关系;不同浓度姜黄素(0、7.5、15、30、60μmol/L)分别处理结肠腺癌细胞SW480和HT29细胞24 h和48 h后,Western blot法检测细胞内NICD1、Notch1及HES-1蛋白的表达情况。结果 NICD1在人结直肠癌组织中均表达,阳性率100%,癌旁肠组织中部分表达,阳性率为90.3%,但癌组织表达强度明显高于癌旁组织,差异有统计学意义(P<0.05);Western blot结果示姜黄素能下调人结肠腺癌细胞SW480及HT29细胞中NICD1、Notch1及HES-1蛋白的表达,有时间和剂量依赖。结论 Notch1信号通路中NICD1蛋白在结直肠癌组织中的过度表达可能与肿瘤的发生发展相关,其阳性表达的部位可能与癌组织的病理分期有关;姜黄素可能通过调控Notch1信号通路抑制结直肠癌细胞增殖。Objective To test the expression of Notchl intracellular domain （NICD1） in human colorectal cancer tissue and to investigate the mechanism of curcumin on the effect of the Notchl pathway in the human colon cancer cells SW480 and HT29. Methods The expression of NICD1 in paraffin section from 40 cases of human colorectal cancer and 31 cases of adjacent tissues were detected by the immunohistochemieal method. The relation of NICD1 with human colorectal cancer was determined by comparing the protein expression rate in intestinal mucosal cells of human colorectal cancer and tissues. The protein expressions of NICD, Notchl and HES-1 in the colon cancer cells SW480 and HT29 which were treated by different concentrations of eurcnmin （0, 7.5, 15, 30, 60 p.mol/L） at 24 h and 48 h, were tested by western blot assay. Results The expression rate of NICD1 in human colorectal cancer tissues was 100%, and the rate in adjacent tissues was 90.3%, the expression rate in colorectal cancer tissues was more significant than that in the adjacent tissues （P〈0.05）. The Weston blot result showed that curcumin could down-regulate the expressions of NICD1, Notchl and HES-1 in SW480 及 HT29 cells with a time-dose independence. Conclusion Over-expression of NICD1 protein in colorectal tissues may be related with the development and progression of cancer. The position of positive expression could be associated with pathological stage of cancer tissues. Cureumin inhibiting proliferation of the eoloreetal cancer cells may relied on down-regulating Notchl pathway.

关 键 词：姜黄素 Notch1通路 NICD 结直肠癌 结肠癌细胞SW480 结肠癌细胞HT29 

分 类 号：R285.6[医药卫生—中药学] R735.37[医药卫生—中医学]