HGF/c-Met信号通路在克唑替尼诱导不同肺癌细胞株凋亡中的作用

被引:5
作者
吕金益 [1 ]
董芷辛 [1 ]
李娅妮 [1 ]
宁瑞玲 [2 ]
宋向群 [2 ]
周韶璋 [2 ]
机构
[1] 广西医科大学附属肿瘤医院
[2] 广西医科大学研究生院
关键词
HGF/c-Met信号通路; H1993细胞; H2228细胞; 克唑替尼; 细胞凋亡;
D O I
暂无
中图分类号
R734.2 [肺肿瘤];
学科分类号
100214 ;
摘要
目的:观察克唑替尼(crizotinib)诱导不同肺癌细胞株凋亡中HGF/c-Met信号通路的变化并探讨其调控机制。方法:采用噻唑蓝(MTT)法检测克唑替尼对H1993(c-Met扩增的肺腺癌细胞)、H2228(含有EML4-ALK融合基因的肺癌细胞)和A549细胞的活力抑制情况;采用流式细胞术检测3种细胞在克唑替尼作用后24 h、48 h和72 h的凋亡率;采用Western blot检测细胞在克唑替尼作用前后HGF/c-Met信号通路中MET蛋白及其磷酸化形式p-MET的水平,同时观察其下游通路关键蛋白AKT、ERK、p-AKT和p-ERK的变化情况。结果:MTT结果表明克唑替尼作用72 h后,H1993、H2228和A549细胞株的细胞活力抑制率均呈剂量依赖性升高。流式细胞术检测发现随着克唑替尼作用时间的延长,细胞凋亡率呈时间依赖性增加(P<0.05)。Western blot检测结果提示在H1993细胞株和H2228细胞株中,p-MET、p-AKT和p-ERK随着时间的延长蛋白水平呈现下降趋势。而在A549细胞株中p-AKT、p-ERK和p-MET在药物作用72 h后的变化趋势不明显。结论:初步证实HGF/c-Met信号通路与克唑替尼诱导肺癌细胞株H1993和H2228凋亡相关。
引用
收藏
页码:445 / 450
页数:6
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