Notch1/Jagged1信号对人肝癌SMMC7721细胞增殖和侵袭的影响及其作用机制  

Role of Notch 1/Jagged 1 signaling in the proliferation and invasion of human hepatoma SMMC 7721 cells

作　　者：岳犇[1] 熊奇如[1] 夏俊[1] 盛华嵩[2] 

机构地区：[1]安徽医科大学第一附属医院普通外科,合肥230022 [2]武警安徽省总队医院普通外科,合肥230000

出　　处：《安徽医科大学学报》2013年第2期128-132,共5页Acta Universitatis Medicinalis Anhui

摘　　要：目的研究激活的Notch 1信号系统对人肝癌SMMC7721细胞增殖和侵袭力的调控,并初步探讨其可能机制。方法体外培养人肝癌SMMC 7721细胞,RT-PCR技术检测细胞中Notch信号系统的表达情况,向人SMMC 7721细胞中分别加入Notch信号通路的激活剂Jagged 1蛋白(激活剂组)、抑制剂γ-分泌酶抑制剂DAPT(抑制剂组),空白对照组加PBS缓冲液。MTT法和软琼脂集落形成试验检测各组细胞增殖的情况,Transwell小室法观察细胞侵袭的能力,RT-PCR检测各组细胞中Hes-1、Bcl-2及Snail基因的表达。结果SMMC 7721细胞中存在Notch 1/Jagged 1信号系统的表达,培养12、24、36、48 h后,激活剂组、抑制剂组与空白对照组的吸光度值比较,差异均有统计学意义(P<0.01)。激活剂组、空白对照组和抑制剂组的细胞侵袭数分别为43.8±6.8、64.6±5.6和90.0±6.9(P<0.05)。激活剂组细胞中Hes-1基因的表达增强,Bcl-2及Snail基因的表达显著降低;相反,抑制剂组细胞的Hes-1基因表达降低,Bcl-2及Snail基因的表达显著增强(P<0.05)。结论 Notch 1/Jagged 1信号通路在人肝癌SMMC 7721细胞的增殖和侵袭中发挥重要的调控作用,其机制初步认为可能与下调抗凋亡基因Bcl-2以及肿瘤转移相关基因Snail的表达有关。Objective To study regulation of the proliferation and invasion of human hepatoma SMMC 7721 cells by activated Notch 1 signaling. Methods Human hepatoma SMMC 7721 cells were cultured. The notch signaling was measured by RT-PCR. The Jagged1, an activator of Notch signaling, and the γ-secretase inhibitor（DAPT） were respectively added into the mediums of human hepatoma SMMC 7721, and PBS buffer was added into the control group. Cell proliferation and growth were detected by MTT assay and formation, cell invasion by Transwell chamber assay and the mRNA levels of Hes-1, Bcl-2 and Snail by RT-PCR. Results Notch 1/Jagged 1 were ex- pressed in SMMC 7721 cells. A value of SMMC 7721 cells cultured for 12,24,36,48 hours in activator group and inhibitor group had statistically significant differences compared with control group （P 〈 0.01 ）. The number of cell invasion in the activator group, in control group and in inhibitor group was respectively 43.8±6.8,64. 6±5.6 and 90.0±6.9 （P 〈 0. 05 ）. Hes-1, Bcl-2, Snail mRNA in activator group and inhibitor group had statistically significant differences compared with control group（ P 〈 0. 05 ）. Conclusion Notchl/Jaggedl signaling pathway plays an important regulating role in the proliferation and invasion of human hepatoma SMMC 7721 cells, and its mecha- nisms may involve down-regulating the expression of the target gene Bcl-2 and Snail.

关 键 词：Notch 1 JAGGED 1信号 肝癌 Bcl-2 SNAIL 

分 类 号：R735.7[医药卫生—肿瘤]