葡萄糖调节蛋白-78在肝癌组织中的表达及其意义分析

Expression and significance of glucose regulatory protein-78 in hepatocellular carcinoma

目的探讨葡萄糖调节蛋白-78(GRP-78)在肝细胞癌(HCC)组织中的表达情况及其对肝癌细胞增殖的影响。方法统计83例肝癌患者的HCC组织、癌旁组织及正常肝组织中GRP-78的阳性表达率。测定不同肝癌细胞系中GRP-78mRNA的相对表达水平,将表达水平最高的肝癌细胞系进行扩增培养。将扩增后的细胞分为未转染的空白组、小干扰RNA(siRNA)-NC组及GRP-78-siRNA组,分析3组细胞的增殖抑制率、凋亡率及磷脂酰肌醇3激酶(PI3K)/丝苏氨酸蛋白激酶(AKT)信号通路中相关蛋白的表达水平。结果3种组织中HCC组织中GRP-78的阳性表达率最高(P<0.05),且与HCC患者的TNM分期呈正相关(P<0.05);在SMMC-7721肝癌细胞系中,GRP-78mRNA的相对表达水平最高;在干扰48h及72h时,GRP-78-siRNA组的细胞抑制率显著高于空白组及siRNA-NC组,差异有统计学意义(P<0.05);而在干扰48h时,GRP-78-siRNA组的细胞凋亡率高于另外两组,差异有统计学意义(P<0.05);与空白组、siRNA-NC组比较,GRP-78-siRNA组的E-cadherin表达升高,vimentin、磷酸化-PI3K(p-PI3K)、磷酸化-AKT(p-AKT)表达降低,组间差异有统计学意义(P<0.05)。结论GRP-78可通过PI3K/AKT信号通路促进肝癌的发生。

Objective To investigate the expression of glucose-regulated protein-78(GRP-78)in hepatocellular carcinoma(HCC)and its effect on the proliferation of liver cancer.Methods The positive expression rate of GRP-78 in HCC tissues,adjacent tissues and normal liver tissues of 83 patients with HCC was analyzed.The relative expression of GRP-78 mRNA in different liver cancer cell lines was measured,and the liver cancer cell line with the highest expression level of GRP-78 were amplified and cultured.The amplified cells were divided into the blank group,the siRNA-NC group and the GRP-78-siRNA group,and the proliferation inhibition rate,apoptosis rate and expression level of related proteins in the PI3 K/AKT signaling pathway were analyzed in the three groups.Results The positive expression rate of GRP-78 in HCC tissues was the highest(P<0.05),and it was positively correlated with TNM stage of HCC patients(P<0.05).The expression of GRP-78 mRNA was the highest in SMMC-7721 cell line.At 48 hand 72 h,the cell inhibition rate of the GRP-78-siRNA group was significantly higher than that of the blank group and the siRNA-NC group(P<0.05).At 48 h,the apoptosis rate of the GRP-78-siRNA group was higher than that of the other two groups(P<0.05).Compared with the blank group and the siRNA-NC group,the expression level of E-cadherin in the GRP-78-siRNA group was increased,while the expression levels of vimentin,p-P13 Kand p-AKT were downregulated,the differences were statistically significant(P<0.05).Conclusion GRP-78 can promote the development of liver cancer through PI3 K/AKT signaling pathway.