中国病理生理杂志Issue(6):1103-1109,7.DOI:10.3969/j.issn.1000-4718.2014.06.025
mTOR 信号通路在克唑替尼诱导的 EML4-ALK融合基因阳性肺癌细胞株 H2228凋亡中的作用
Role of mTOR signaling pathway in crizotinib-induced apoptosis of EML4-ALK fusion gene-positive lung adenocarcinoma cell line H2228
摘要
Abstract
AIM:To investigate the mammalian target of rapamycin ( mTOR) signaling pathway as the center playing a role in the crizotinib-induced apoptosis of non-small cell lung cancer (NSCLC) cell line H2228, which represents positive echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene. METHODS:H2228 cells were processed according to different purposes .Fluorescence quantitative PCR is used to ob-serve the gene states .MTT assay is used to detect the cell inhibition rates .The cell apoptosis and cell cycle were analyzed by flow cytometry .The expression and activation levels of the key proteins in the mTOR signaling pathway were determined by Western blotting .RESULTS:Crizotinib promoted the apoptosis of H 2228 cells in a time-and dose-dependent manner . Crizotinib blocked the H2228 cells staying at the G1 phase.In apoptotic H2228 cells processed with crizotinib, the activa-tion level of mTOR was decreased , and the activation levels of the key proteins in upstream and downstream of mTOR path -way were both declined .The expression level of the fusion protein EML 4-ALK variant 3 was not affected , but its active form of p-ALK was significantly suppressed .CONCLUSION:mTOR signaling pathway has a certain relationship with the crizotinib-induced apoptosis of lung cancer cell H 2228, which represents positive EML4-ALK fusion gene.关键词
EML4-ALK融合基因/H2228细胞/克唑替尼/细胞凋亡/哺乳动物雷帕霉素靶蛋白Key words
EML4-ALK fusion gene/H2228 cells/Crizotinib/Apoptosis/Mammalian target of rapamycin分类
医药卫生引用本文复制引用
戴辉,宋向群,潘星辰,彭海燕,韦江,周韶璋..mTOR 信号通路在克唑替尼诱导的 EML4-ALK融合基因阳性肺癌细胞株 H2228凋亡中的作用[J].中国病理生理杂志,2014,(6):1103-1109,7.基金项目
国家自然科学基金资助项目(No.81060188);广西科技厅项目 ()