突触结合蛋白-7通过Chk1-P53信号通路促进肝癌细胞增殖研究  

Study on the promotion of HCC cell proliferation by synaptic binding protein-7 through the Chk1-P53 signaling pathway

作　　者：金浩[1] 庞青 谈燚[1] 刘会春[1] 王勇[1] 满忠然[1] JIN Hao;PANG Qing;TAN Yi;LIU Huichun;WANG Yong;MAN Zhongran(Department of Hepatobiliary Surgery,the First Affiliated Hospital of Bengbu Medical College,Anhui 233004,China)

机构地区：[1]蚌埠医学院第一附属医院肝胆外科

出　　处：《现代医药卫生》2019年第19期2939-2945,2948,共8页Journal of Modern Medicine & Health

基　　金：安徽省教育厅2019年度高校自然科学研究资助重点项目(KJ2019A0294);2017年蚌埠医学院科技发展基金资助项目(BYKF1738);蚌埠医学院第一附属医院2017年度科技发展基金资助项目(byyfykj201708)

摘　　要：目的通过检测突触结合蛋白-7(Syt-7)表达,研究其在肝细胞癌(HCC)中的作用,并阐明其潜在的机制。方法通过实时荧光定量聚合酶链式反应检测肝癌细胞和正常肝细胞中Syt-7mRNA表达水平。通过Celigo细胞计数、MTT检测、克隆检测和细胞周期分析评估体外敲低Syt-7的效果。通过裸鼠模型评价体内成瘤效果。应用PathScan应激和凋亡信号传导抗体阵列试剂盒评估潜在的分子机制。结果Syt-7mRNA在肝癌细胞Huh-7和Hep3B中高表达,在肝癌细胞SMMC-7721、HepG2和BEL-7402中适度表达,在人正常肝细胞L-O2中低表达。功能实验表明,敲低Syt-7可通过增加Chk1和P53磷酸化明显抑制细胞增殖和诱导细胞周期停滞。此外,敲低Syt-7可显著抑制裸鼠的体内成瘤。结论Syt-7在HCC肿瘤形成和进展中起着重要作用,可能成为HCC新的治疗靶点。Objective To investigate the role of synaptic binding protein-7(Syt-7)in hepatocellular carcinoma(HCC)by detecting its expression and elucidate its potential mechanism.Methods The expression levels of Syt-7 mRNA in liver cancer cells and normal liver cells were detected by RT-qPCR.Celigo cell count,MTT detection,clone detection and cell cycle analysis were used to evaluate the effect of low Syt-7 in vitro.Tumor formation in vivo was evaluated by nude mouse model.Application PathScan Antibody Array Kit to evaluate potential molecular mechanisms.Results The mRNA of Syt-7 was highly expressed in hepatocellular carcinoma cells Huh-7 and Hep3B,moderately expressed in hepatocellular carcinoma cells SMMC-7721,HepG2 and BEL-7402,and poorly expressed in normal hepatocellular carcinoma cells L-O2.Functional experiments showed that knockdown of Syt-7 significantly inhibited cell proliferation and induced cell cycle arrest by increasing phosphorylation of Chk1 and P53.In addition,knockdown of Syt-7 significantly inhibited tumor formation in nude mice.Conclusion Syt-7 plays an important role in tumor formation and progression of HCC and may be a new therapeutic target for HCC.

关 键 词：肝细胞肝癌 突触结合蛋白-7 CHK1 P53 细胞周期 

分 类 号：R735.7[医药卫生—肿瘤]