水飞蓟宾调控STAT3信号通路对肝癌细胞增殖和侵袭的影响  

Effect of silybin on invasion and proliferation of hepatocellular carcinoma cell by regulating of STAT3 signaling pathway

作　　者：王金彩[1] 王淑雨 刘小红[1] 路平[3] 李小瑞[3] WANG Jincai;WANG Shuyu;LIU Xiaohong;LU Ping;LI Xiaorui(Department of Pharmacy;Department of Pharmacy, Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450001, He’nan, China;Department of Oncology, the First Affiliated Hospital of Xinxiang Medical College, Xinxiang 453100, He’nan,China)

机构地区：[1]新乡医学院第一附属医院药学部,河南新乡453100 [2]郑州大学医学科学院药理系,郑州4500010 [3]新乡医学院第一附属医院肿瘤科,河南新乡453100

出　　处：《癌症进展》2018年第14期1746-1749,共4页Oncology Progress

摘　　要：目的研究水飞蓟宾调控信号转导及转录激活因子3(STAT3)信号通路对肝癌细胞增殖和侵袭能力的影响。方法采用0、50、100、200和400μmol/L的水飞蓟宾作用于肝癌细胞HepG2,噻唑蓝(MTT)检测细胞存活率,计算半数抑制浓度(IC50)。采用200μmol/L的水飞蓟宾作用于肝癌细胞,Transwell小室检测侵袭细胞数目,蛋白质印迹法(Western blot)检测细胞中STAT3、磷酸化的STAT3(p-STAT3)、基质金属蛋白酶-9(MMP-9)的表达水平。根据处理方法不同,将肝癌细胞分为未处理组、药物作用组和激活剂组,其中未处理组不加入任何药物,药物作用组细胞培养液中加入200μmol/L的水飞蓟宾,激活剂组在药物作用组的基础上再加入8μmol/L的STAT3通路激活剂SD19。将3组细胞培养48 h后,MTT检测细胞存活率,Transwell小室检测侵袭细胞数目,Western blot检测细胞中STAT3、p-STAT3、MMP-9蛋白的表达水平。结果 50、100、200和400μmol/L的水飞蓟宾处理后,肝癌细胞的存活率逐渐下降,IC50为(198.64±25.61)μmol/L。采用200μmol/L的水飞蓟宾作用的肝癌细胞后,侵袭细胞数目为(96.35±13.24),明显少于0μmol/L的水飞蓟宾作用后的(192.58±13.64),差异有统计学意义(P﹤0.01)。与0μmol/L的水飞蓟宾作用的肝癌细胞相比,200μmol/L的水飞蓟宾作用于肝癌细胞后,pSTAT3和MMP-9蛋白表达水平均明显下降,差异均有统计学意义(P﹤0.01)。激活剂组的细胞存活率、侵袭细胞数目及p-STAT3和MMP-9蛋白表达水平均明显高于药物作用组,差异均有统计学意义(P﹤0.01)。结论水飞蓟宾可抑制肝癌细胞的增殖和侵袭,作用机制可能与STAT3信号通路有关。Objective To investigate the effects of silybin on invasion and proliferation of hepatocellular carcinoma cell by regulating signal transduction and transcription factor3(STAT3)signaling pathway.Method Silybin was applied to hepatocellular carcinoma cell line HepG2at concentration of0,50,100,200,400μmol/L,then the survival rate of cells was detected by MTT and the IC50was calculated.Silybin was applied to hepatocellular carcinoma cells at concentration of200μmol/L,then the invasive cells was detected by Transwell cell assay and the expression levels of STAT3,p-STAT3and MMP-9in the cells was detected by Western blot.According to the different processing method,the hepatocellular carcinoma cells were divided into untreated group(applied without any medication),medication group(applied with silybin at concentration of200μmol/L)and activator group(applied with SD19,the activator of STAT3signaling pathway,at concentration of8μmol/L based on silybin at concentration of200μmol/L).After cultured for48h,the cells proliferation was detected by MTT,the cell invasion was examined by Transwell cell assay,the expression levels of STAT3,p-STAT3and MMP-9in the cells was detected by Western blot.Result After treatment with silybin at concentration of50,100,200and400μmol/L,the survival rate of hepatocellular carcinoma cells decreased gradually.The calculated IC50was(198.64+25.61)μmol/L.After treated by silybin at concentration of200μmol/L,the number of invasive cells was(96.35±13.24),which was significantly lower than that(192.58±13.64)of treated by silybin at concentration of0μmol/L,the difference was statistically significant(P<0.01).Compared with those of hepatocellular carcinoma cells treated by silybin at concentration of0μmol/L,the expression of p-STAT3and MMP-9in hepatocellular carcinoma cells significantly decreased after treated by silybin at concentration of200μmol/L(P<0.01).The cell viability,the number of invasive cells and the expression of p-STAT3and MMP-9protein in the cells of activator group were all

关 键 词：肝癌 增殖 侵袭 水飞蓟宾 

分 类 号：R735.7[医药卫生—肿瘤]