西妥昔单抗对非小细胞肺癌A549细胞的抗肿瘤效应及其机制探讨  

Effect of cetuximab on proliferation and gene expression of A549 cells and its underlying mechanism

作　　者：李瑾昱[1] 张国庆[1] 焦顺昌[1] 温新宇[1] 孙胜杰[1] 

机构地区：[1]解放军总医院肿瘤内科,北京100853

出　　处：《解放军医学杂志》2013年第9期738-742,共5页Medical Journal of Chinese People's Liberation Army

基　　金：国家科技支撑计划(2009BAI86B05)~~

摘　　要：目的探讨西妥昔单抗对K-ras突变的非小细胞肺癌A549细胞的体外生长抑制及凋亡诱导作用。方法采用CCK-8法及流式细胞仪分别检测西妥昔单抗对A549细胞的生长抑制作用及凋亡诱导情况;通过基因芯片检测技术比较西妥昔单抗作用组与对照组K-ras突变的A549细胞肿瘤相关基因表达的差异。结果西妥昔单抗对K-ras突变的A549细胞具有生长抑制及凋亡诱导作用。西妥昔单抗作用后,有10个基因表达显著上调,9个基因表达显著下调。Real-timePCR检测验证西妥昔单抗作用后STAT1基因及IGFBP3基因表达显著上调。结论西妥昔单抗对K-ras基因突变的肺腺癌A549细胞具有生长抑制及凋亡诱导作用,STAT1和IGFBP3基因表达上调可能与西妥昔单抗对非小细胞肺癌的作用机制相关。Objective To investigate the effect of cetuximab on inhibition of proliferation and apoptosis of A549 cells with K-ras mutation.Methods The inhibition of proliferation and apoptosis rate of A549 cells induced by cetuximab were analyzed by CCK-8 assay and flow cytometry,respectively.The disparity on gene expression of A549 cells was compared between cetuximab group and control group by microarray.Results Treatment with cetuximab resulted in inhibition of proliferation and apoptosis of A549 cells with K-ras mutation.There were 10 genes upregulated and 9 genes downregulated after cetuximab treatment.Realtime PCR confirmed that the gene expressions of STAT1 and IGFBP3 of A549 cells were upregulated obviously after cetuximab treatment.Conclusions Cetuximab may have an inducing effect on inhibition of proliferation and apoptosis on non-small cell lung cancer cell line A549 which has undergone K-ras mutation.STAT1 and IGFBP3 up-regulation may be one of the mechanisms underlying inhibitory effect of ceturimab on NSCLC.

关 键 词：西妥昔单抗 基因 K-ras 寡核苷酸序列分析 STAT1转录因子 胰岛素样生长因子结合蛋白质3 

分 类 号：R734.2[医药卫生—肿瘤]