低浓度MNK1抑制剂CGP57380可抑制人肺腺癌细胞增殖并诱导其凋亡  

Low concentration of MNK1 inhibitor CGP57380 inhibits the proliferation of human lung adenocarcinoma A549 cells and induces their apoptosis

作　　者：苏小元[1] 刘斌[1] 

机构地区：[1]广州医科大学附属广州市第十二人民医院中心实验室,广东广州510620

出　　处：《肿瘤》2013年第10期873-878,共6页Tumor

基　　金：广州市卫生局重大民生攻关专项基金资助项目(编号:2012Y2-00029)

摘　　要：目的：观察低浓度的丝裂原活化蛋白激酶相互作用激酶1（mitogen—activatedproteinkinase—interactingkinase1，MNKl）抑制剂CGP57380对人肺腺癌A549细胞增殖和凋亡的影响。方法：应用低浓度（1～4gmol／L）CGP57380作用A549细胞24～72h后，采用MTS法检测细胞的增殖抑制情况，FCM法检测细胞周期和细胞凋亡变化，蛋白质印迹法检测磷酸化MNKl（phosphorylatedMNKl，p-MNKl）和磷酸化人类真核翻译起始因子4E（phosphorylatedhumaneukaryotictranslationinitiationfactor4E，p-eIF4E）蛋白的表达水平。结果：与未经药物处理对照组相比，1～4μmol／L的CGP57380作用48h后均能抑制A549细胞的增殖（P〈0．05）；2～4μmol／L的CGP57380可在72h后使细胞周期阻滞于G2／M期（P〈0．05）。各种浓度的CGP57380均可使细胞凋亡率明显增加（P〈0．05），且药物浓度越高，出现凋亡的时间越早。1μmol／LCGP57380作用48h后，A549细胞中P-MNK和p-eIF4E蛋白的表达明显低于对照组（P〈0．05）。结论：低浓度CGP57380能抑制人肺腺癌A549细胞的增殖并诱导其凋亡，MNK1基因可能成为新的肺癌治疗靶点。Objective： To observe the effects of low concentration of CGP57380, an inhibitor of mitogen-activated protein kinase-interacting kinase 1 （MNK1） on the proliferation and apoptosis of human lung adenocarcinoma A549 cells. Methods： A549 cells were treated with low concentrations （1-4 μmol/L） CGP57380 for 24-72 hours, then the cell proliferation was assessed by MTT assay, and the apoptosis and cell cycle distribution were detected by flow cytometry. The expression levels of phosphorylated MNK1 （p-MNK1） and phosphorylated human eukaryotic translation initiation factor 4E （p-elF4E） proteins in A549 cells treated with 1μmol/L CGP57380 for 48 hours were examined by Western blotting. Results： Comparing to the control, the proliferation of A549 cells was inhibited after treatment with different concentrations of CGP57380 for 48 hours （all P 〈 0.05）. A549 cells treated with 2-4μmol/L CGP57380 for 72 hours were induced G2/M cell cycle arrest （both P 〈 0.05）. CGP57380 at different concentrations could induce dose-dependent apoptosis in A549 cells. The expression levels of p-MNK1 and p-elF4E were significantly lower in A549 cells treated with 1 μmol/L CGP57380 than those in the control （P 〈 0.05）. Conclusion： Low concentration of CGP57380 can inhibit the proliferation of human lung adenocarcinoma A549 cells and induce their apoptosis, implying that MNK1 gene may be a candidate target for the treatment of lung cancer.

关 键 词：肺肿瘤 受体作用蛋白丝氨酸苏氨酸激酶类 丝裂原活化蛋白激酶 真核细胞起始因子4E 细胞增殖 细胞凋亡 蛋白酶抑制药 CGP57380 

分 类 号：R734.2[医药卫生—肿瘤]