鼻咽癌中表皮生长因子受体与相关信号蛋白关系及对细胞增殖的影响  

Relationship between epidermal growth factor receptor and the correlated-signal proteins in nasopharyngeal carcinoma and its effects on cell proliferation

作　　者：赵颖海[1] 景志亮[1] 李飞虹[1] 

机构地区：[1]广东医学院病理学教研室,广东湛江524023

出　　处：《生物医学工程与临床》2011年第5期475-478,F0003,共5页Biomedical Engineering and Clinical Medicine

基　　金：湛江市第四批科技攻关项目(2010C3104004)

摘　　要：目的研究表皮生长因子受体（EGFR）与细胞增殖相关信号分子p-ERK、c-fos、Ki-67在鼻咽癌及鼻咽黏膜上皮中表达的关系及其抑制剂西妥昔（Cetuximab）对鼻咽癌CNE-2Z细胞增殖的影响。方法用链霉菌抗生物素蛋白-过氧化物酶（SP）法检测30例鼻咽癌（男性22例,女性8例;年龄28~70岁,中位年龄49岁）、23例（男性15例,女性8例;年龄21~68岁,中位年龄40岁）鼻咽黏膜慢性炎症患者病变部位EGFR、磷酸化细胞外信号调节激酶（p-ERK）、c-fos、Ki-67蛋白的表达。设立不同对照组和实验组,实验组分别用不同质量浓度西妥昔（0.1、0.2、0.5 mg/mL）作用于CNE-2Z细胞48 h,用噻唑蓝（MTT）比色法检测细胞增殖,SP法检测EGFR、p-ERK、c-fos和Ki-67蛋白的表达。结果 EGFR、p-ERK、c-fos和Ki-67蛋白在鼻咽癌阳性表达率分别为86.67%（26/30）、93.33%（28/30）、83.33%（25/30）、86.67%（26/30）,在鼻咽黏膜慢性炎症上皮阳性表达率分别为30.43%（7/23）、26.09%（6/23）、17.39%（4/23）、4.35%（1/23）,组间差异有显著统计学意义（P〈0.01）;鼻咽癌中EGFR表达与p-ERK、c-fos、Ki-67表达呈正相关（P〈0.05）。不同质量浓度西妥昔分别作用于CNE-2Z细胞48 h,细胞增殖受抑制,组间差异有显著统计学意义（P〈0.01）,EGFR、p-ERK、c-fos、Ki-67蛋白表达减少。结论鼻咽癌中EGFR蛋白表达可能参与调控细胞增殖;质量浓度0.2 mg/mL可能是西妥昔体外抑制鼻咽癌细胞增殖的效应浓度,西妥昔可望用于鼻咽癌的靶向治疗。Objective To investigate the relationship of epidermal growth factor receptor（EGFR） expression with phosphorylated extracellular-signal regulated protein kinase（p-ERK）,c-fos,Ki-67 signal proteins in nasopharyngeal cancer（NPC） and nasopharyngeal mucosal epithelia,and study the effect of Cetuximab（monoclonal antibody against EGFR） on the proliferation of NPC CNE-2Z cells.Methods Immunocytochemical SP method was adopted to detect the expression of EGFR,p-ERK,c-fos and Ki-67 protein in NPC cells from 30 patients（male 22,female 8;aged 28-70 years old,median age 49 years old） and nasopharyngeal mucosal epithelia from 23 patients（male 15,female 8;aged 21-68,median age 40 years old）.CNE-2Z cells were divided into experimental group and control group.The experimental group was treated with different doses of Cetuximab（0.1 mg/mL,0.2 mg/mL and 0.5 mg/mL,respectively）.Methyl thiazolyl tetrazolium（MTT） assay was employed to evaluate the proliferation of CNE-2Z cells.Immunocytochemical SP method was utilized to detect the expression of EGFR,p-ERK,c-fos and Ki-67 protein.Results The positive staining rate of EGFR,p-ERK,c-fos and Ki-67 protein in 30 cases of NPC was 86.67 %（26/30）,93.33 %（28/30）,83.33 %（25/30） and 86.67 %（26/30）,respectively,whereas the positive staining rate of the 4 proteins in 23 cases of nasopharyngeal mucosal epithelia was 30.43 %（7/23）,26.09 %（6/23）,17.39 %（4/23） and 4.35 %（1/23）,respectively.The expression of the 4 proteins in 2 groups had statistically significant difference（P 〈 0.01）.The expression of EGFR was positively correlated with that of p-ERK,c-fos,Ki-67 protein by Spearman correlation analysis（P 〈 0.05）.MTT results demonstrated that the proliferation of CNE-2Z cells was significantly inhibited by treatment with Cetuximab for 48 hours（P 〈 0.01）.Decrease in the expression of EGFR,p-ERK,c-fos and Ki-67 protein was observed in the CNE-2Z cells treated with Cetuximab.Conclusion It is demonstrated that EGFR protein coul

关 键 词：鼻咽癌 表皮生长因子受体 增殖 西妥昔单抗 

分 类 号：R739.63[医药卫生—肿瘤]