表皮生长因子受体表达与非小细胞肺癌放疗敏感性的关系  

Relationship between epidermal growth factor receptor gene expression and radiosensitivity of non- small-cell lung cancer cells

作　　者：张敏[1] 牟晓燕[1] 姜淑娟[1] 刘庆亮[1] 李道卫[1] 

机构地区：[1]山东省立医院呼吸内科,济南250021

出　　处：《中华肿瘤杂志》2013年第2期94-97,共4页Chinese Journal of Oncology

基　　金：山东省自然科学基金攻关项目（2010GSF10253）

摘　　要：目的探讨表皮生长因子受体（EGFR）表达与非小细胞肺癌（NSCLC）放疗敏感性的关系。方法体外化学合成EGFR基因序列特异性双链RNA（dsRNA）结合脂质体Lipofectamine2000转染肺腺癌细胞株SPC—A1，采用实时荧光定量PCR（real—timePCR）和Wesemblot法测定转染细胞中EGFRmRNA和蛋白的表达，采用集落抑制实验观察EGFR序列特异性dsRNA（dsRNA—EGFR）的体外放疗增敏作用。建立裸鼠肿瘤模型，通过测定肿瘤体积和肿瘤重量，绘制肿瘤生长曲线，计算肿瘤抑制率。结果对照组、dsRNA．unrelated组和dsRNA—EGFR组的EGFRmRNA相对表达量分别为1．51±0．22、1．38±0．15和0．45±0．11（F=482．7，P〈0．01），EGFR蛋白表达水平分别为2340．87±10．99、2231．85±35．66和832．03±39．13（F=263．3，P〈0．05）。dsRNA—EGFR可将对照组EGFRmRNA和蛋白水平分别下调70．2％和64．5％。放疗对照组、dsRNA-unrelated联合放疗组和dsRNA-EGFR联合放疗组的集落抑制率分别为9．3％、12．5％和65．5％，肿瘤抑制率分别为21．3％、24．4％和64．2％，dsRNA-EGFR联合放疗可显著抑制体外、体内的肿瘤生长。结论dsRNA—EGFR可显著抑制NSCLC中EGFRmRNA和蛋白的表达．有效抑制肿瘤牛长,增强NSCLC的放疗敏感性。Objective To explore the relationship between epidermal growth factor receptor（EGFR） gene expression and radiosensitivity of non-small-cell lung cancer （NSCLC） cells. Methods EGFR sequence-specific double-stranded RNA （dsRNA-EGFR） was chemically synthesized. NSCLC cell line SPC- A1 was transfected with dsRNA-EGFR formulated with Lipofectamine 2000. Western blot and real-time PCR were used to determine the EGFR mRNA and protein expression, respectively. Colony inhibition test was adopted to observe the radiosensitizing effect. To establish the nude mouse tumor models, calculate the tumor growth inhibition rate and make the tumor growth curve by measuring its size and weight. Results EGFR mRNA levels were 1.51 ± 0.22, 1.38 ± 0.15 and 0. 45 ± 0.11 in the control group, dsRNA-unrelated group and dsRNA-EGFR group, respectively （F =482.7 ,P 〈0.01 ）. The contents of EGFR protein were 2340.87 ± 10.99, 2231.85 ±35.66 and 832.03 ± 39.13 in the control group, dsRNA-unrelated group and dsRNA- EGFR group, respectively （ F = 263.3, P 〈 0.05 ）. Compared with the control group, dsRNA-EGFR sequence specifically decreased the expressions of EGFR mRNA by 70.2% and EGFR protein by 64.5%. The colony inhibition rates of the control group, dsRNA-unrelated combined with radiotherapy group mad dsRNA-EGFR combined with radiotherapy group were 9.3%, 12.5% and 65.5%, and the tumor growth inhibition rates were 21. 3%, 24.4% and 64. 2%, respectively. The combination of dsRNA-EGFR and radiotherapy significantly inhibited the tumor growth in vitro and in vivo. Conclusions DsRNA-EGFR shows an apparent inhibitory effect on the expression of EGFR mRNA and protein of NSCLC eells, effectively inhibit the tumor growth in vivo, and enhance the radiosensitivity of NSCLC.

关 键 词：肺肿瘤 表皮生长因子受体 RNA 双链 放射敏感性 

分 类 号：R734.2[医药卫生—肿瘤]