鼻咽癌细胞PI3K/AKT和ERK/MAPK信号通路活性表达及其临床意义的探讨

Expression of insulin-like growth factor-1 receptor,activation of PI3K/AKT and ERK/MAPK signal transduction pathway in nasopharyngeal cancer cells

目的:探讨鼻咽癌细胞中PK3K/AKT和ERK/MAPK信号传导通路异常激活与鼻咽癌细胞发生发展的关系。方法:蛋白质印迹法检测3例鼻咽低分化鳞癌组织及其细胞株(CNE2)和鼻咽炎性组织中IGF-1R、AKT和ERK1/2蛋白的表达情况;相同实验方法检测鼻咽癌细胞株CNE2中磷酸化的PAKT和pERK1/2蛋白的表达和给予胰岛素样生长因子-1(IGF-1)刺激癌细胞后磷酸化的pAKT和pERK的表达水平,再分别用PKB/AKT和ERK/MAPK通路抑制剂对CNE2细胞信号传导通路磷酸化的调节作用进行抑制试验。结果:3例鼻咽低分化鳞癌组织和CNE2细胞株中IGF-1R、AKT和ERK1/2蛋白表达水平明显高于鼻咽炎性组织;IGF-1可刺激CNE2细胞中pAKT和pERK1/2的表达增加,与空白对照组相比,其pAKT和pERK表达量明显增高;给予Wort-mannin和PD98059治疗24和48h后,CNE2细胞株生长明显受到抑制。结论:IGF-1R的过度表达及其PK3K/AKT、ERK/MAPK信号传导通路的异常激活在鼻咽癌的发生、发展过程中可能起着非常重要的作用,IGF-1R系统有可能作为复发或转移性鼻咽癌治疗中一个潜在的靶分子。

OBJECTIVE： To study the effect of treatment with PI3K/AKT and ERK/MAPK specific inhibitors in the human nasopharyngeal cancer cells and evaluate the relationship be tween them. METHODS： Protein expressions of IGF-1R and its downstream AKT, ERK1/2 in human nasopharyngeal low differentiated squamous epithelium carcinoma cell and its cell line CNE2 and in control nasopharngotis tissues were examined by Western blots; and the regulations of IGF-1 stimulation, PI3K/AKT and ERK/MAPK specific inhibitors Wortmannin and PD98059, AKT and ERK1/2 phosphorylation were also detected on the cell line CNE2. Meanwhile, the cell viability was assessed by the XTT assay. RESULTS： The protein levels of IGF-1R, AKT and ERK1/2 were significantly higher in nasopharyngeal cancer cell and its cell line CNE2 than in the control nasopharngo tis tissues. The expressions of pAKT/AKT and p ERK/ERK1/2 were strongly associated with the overexpression of IGF-1R. IGF-1 stimulation induced more p-ERK1/2 and p-AKT activation in nasopharyngeal cancer cell line （CNE2） than that in its control （without IGF-1）. Upon the treatment with PD98059 or Wort mannin, the cells responsed promptly with decreased ERK1/2 or AKT phosphorylation followed by growth arrest. CONCLUSIONS： The expression of IGF-1R and the activation of pAKT and pERK1/2 pathway seem to play an important role in the pathogenesis of nasopharyngeal cancer. The IGF-1R system might be a potential therapeutic target in nasopharyngeal cancer.