钙黏蛋白与表皮生长因子受体酪氨酸激酶抑制剂治疗肝细胞癌敏感性的相关性  

Association between E-cadherin and sensitivity of hepatocellular carcinoma to treatment with epidermal growth factor receptor tyrosine kinase inhibitor

作　　者：邢荣春[1] 郑军[1] 陈平[1] 郑卫红[2] 刘伟[1] 何政[1] 姚汝铖[1] 

机构地区：[1]三峡大学第一临床医学院普通外科,宜昌443003 [2]三峡大学医学院药理学教研室,宜昌443002

出　　处：《第二军医大学学报》2014年第8期915-919,共5页Academic Journal of Second Military Medical University

摘　　要：目的探讨钙黏蛋白(E-cadherin)表达在表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)治疗肝细胞癌耐药形成中的作用。方法选取常见的4种肝细胞癌细胞HepG2、BEL-7404、SK-HEP-1和MHCC97,用蛋白质印迹法检测这4种肝癌细胞中E-cadherin的蛋白表达,MTT法检测E-cadherin的表达与肝癌细胞EGFR-TKI治疗抑制率的相关性。结果 4种肝癌细胞中HepG2、BEL-7404表达E-cadherin呈阳性并对EGFR-TKI治疗敏感,PD153035和吉非替尼两种EGFR-TKI的药物浓度与肝癌细胞HepG2、BEL-7404的生存率之间存在相关性(P<0.05);然而,肝癌细胞SK-HEP-1和MHCC97中E-cadherin表达阴性并对EGFR-TKI治疗耐药,PD153035和吉非替尼两种药物浓度与肝癌细胞MHCC97、SK-HEP-1的生存率之间不存在相关性(P>0.05)。另外,E-cadherin表达阴性细胞SK-HEP-1转染E-cadherin目的基因后与转入空载体的肝癌细胞相比,EGFR-TKI治疗的敏感性上调(P<0.05)。结论 E-cadherin在调节EGFR分子靶向治疗的敏感性方面起重要作用。Objective To investigate the role of E-cadherin in resistance of hepatocellular carcinoma to treatment with epidermal growth factor receptor tyrosine kinase inhibitor （EGFR-TKI）. Methods Four liver cancer cell lines were used in the present study, namely, HepG2, BEL-7404, SK-HEP 1 and MHCC97. E-cadherin protein expression in the four cell lines was examined by Western blotting analysis. MTT method was used to examine the relationship between E-cadherin expression and inhibition rates of liver cancer cells treated with EGFR-TKI. Results E-cadherin was positive in HepG2 and BEL 7404 cells, and they were sensitive to EGFR-TKI treatment; the survival rates of HepG2 and BEL-7404 cells were correlated with the concentrations of PD153035 and gefitinib （P〈0.05）. E-cadherin was negative in SK-HEP-1 and MHCC97 cells, and they were both resistant to EGFR-TKI treatment, and there was no association between SK-HEP-1 and MHCC97 cell survival rates and concentrations of PD153035 and gefitinib （P 〉 0. 05）. The sensitivity of SK-HEP-1 cells to EGFR-TKI was significantly increased after transfected with E-cadherin compared with those transfected with empty vectors（P〈0. 05）. Conclusion E- cadherin plays an important role in regulating the sensitivity of EGFR molecule targeted therapy.

关 键 词：钙黏蛋白 表皮生长因子 酪氨酸激酶抑制剂 肝细胞癌 肿瘤抗药性 

分 类 号：R735.7[医药卫生—肿瘤]