Shp2在肺腺癌细胞A549中的抑癌作用及机制研究  

Anticancer function of Shp2 in lung adenocarcinoma A549 cells and related molecular mechanisms

作　　者：陆志伟[1] 程玉生[1] 赵春阳[1] 王寒黎 

机构地区：[1]皖南医学院第一附属医院呼吸内科,安徽芜湖241001

出　　处：《中国病理生理杂志》2016年第9期1589-1593,共5页Chinese Journal of Pathophysiology

基　　金：皖南医学院引进人才基金资助项目(No.YR201107);皖南医学院中青年基金资助项目(No.WK2014F43)

摘　　要：目的:探索Shp2在肺腺癌细胞A549中的抑癌作用及机制。方法:应用CCK-8及Ed U实验检测Shp2特异性抑制剂Phps-1抑制Shp2活性对A549细胞活力、增殖及对顺铂(DDP)耐药情况的影响,Annexin VFITC/PI双染法检测细胞凋亡率,Western blot法检测caspase-3的17 kD片段(caspase-3-17p)、Bcl-2、Bax、p-STAT3/STAT3及p-ERK/ERK的蛋白水平。结果:Phps-1浓度为20μmol/L、作用24 h对A549细胞活力的促进作用显著,与对照组比较具有显著性统计学差异(P<0.05)。Phps-1 20μmol/L组的细胞增殖率为0.455±0.085,对照组为0.307±0.012。DDP 8 mg/L组及Phps-1 20μmol/L联合DDP 8 mg/L组的细胞凋亡率分别为13.01%±2.62%和3.67%±0.93%(P<0.05)。抑制Shp2活性能够下调DDP诱导的促凋亡蛋白caspase-3-17p及Bax的蛋白水平,并上调p-STAT3及下调p-ERK蛋白水平。结论:Shp2在肺腺癌细胞A549中具有抑癌作用,抑制STAT3信号通路激活可能是Shp2发挥抑癌作用的重要分子机制。AIM： To explore the anticancer function of Shp2 in lung adenocarcinoma A549 cells and the related molecular mechanisms. METHODS： The viability and proliferation of A549 cells treated with Shp2 specific inhibitor Phps-1 or cisplatin（ DDP） were measured by CCK-8 assay and Ed U assay. Annexin V-FITC / PI double staining was applied to detect apoptotic rate of A549 cells with different interventions. The protein levels of caspase-3-17 p,Bcl-2,Bax,pSTAT3 / STAT3 and p-ERK / ERK were determined by Western blot. RESULTS： Compared with control group,Phps-1 at the concentration of 20 μmol / L significantly increased the viability of A549 cells after 24 h of treatment（ P〈0. 05）.Meanwhile,the proliferation rate of A549 cells in Phps-1 20 μmol / L group was significant increased compared with control group（ P〈0. 05）. The apoptotic rate of A549 cells in DDP treatment group decreased from 13. 01% ± 2. 62% to 3. 67%± 0. 93% after adding Phps-1（ P〈0. 05）. Phps-1 down-regulated the protein levels of caspase-3-17 p,Bax and p-ERK,but up-regulated p-STAT3. CONCLUSION： Shp2 is a tumor suppressor in A549 cells,which may be associated with the activation of STAT3 signal pathway.

关 键 词：Shp2 肺癌 细胞凋亡 

分 类 号：R734.2[医药卫生—肿瘤] R730.23[医药卫生—临床医学]