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机构地区:[1]上海交通大学附属第六人民医院肺内科,上海200233 [2]上海市肺科医院肿瘤科,上海200433
出 处:《肿瘤》2011年第12期1077-1081,共5页Tumor
摘 要:目的:观察索拉非尼对人非小细胞肺癌(non-small cell lung cancer,NSCLC)A549和H1299细胞增殖和凋亡的影响,并探讨其可能机制。方法:不同浓度索拉非尼作用A549和H1299细胞后,应用CCK-8(cellcountingkit-8)法检测细胞的增殖抑制率,FCM检测细胞周期和细胞凋亡,蛋白质印迹法检测细胞的磷酸化细胞外信号调节激酶(phosphorylated extracellular signal-regulated kinase,p-ERK)和磷酸化Ak(tphosphorylated Akt,p-Akt)蛋白的表达水平。结果:不同浓度索拉非尼能抑制A549和H1299细胞的增殖,且呈浓度依赖性(P<0.05);索拉非尼能诱导细胞凋亡,与对照组比较,G0/G1期细胞比率明显上升,S期细胞比率相应下降,细胞阻滞于G0/G1期(P<0.05);索拉非尼作用后,A549和H1299细胞中p-ERK蛋白的表达明显低于对照组(P<0.05)。结论:索拉非尼能抑制人NSCLCA549和H1299细胞的增殖并诱导其凋亡,其作用机制可能与阻断ERK信号通路有关。Objective: To observe the effects of sorafenib on the proliferation and apoptosis of human non-small cell lung cancer (NSCLC) A549 and H1299 cells and to explore their possible mechanisms. Methods: The A549 and H1299 cells were treated with sorafenib at different concentrations. The inhibitory rate of cell proliferation was assessed by cell counting kit-8 (CCK-8). The apoptosis and the cell cycle distribution were analyzed by flow cytometry (FCM). The expression levels of phosphorylated extracellular signal-regulated kinase (p-ERK) and phosphorylated-Akt (p-Akt) proteins in A549 and H1299 cells were examined by Western blotting. Results: The proliferation of A54g and H1299 cells was inhibited via treatment with different concentrations of sorafenib in a dose-dependent manner (P〈O.05). Sorafenib can induce apoptosis. The percentage of cells at G0/G1 phase was significantly increased, and which at S phase was significantly decreased in sorafenib-treated group, as compared with those in the control group (P〈0.05). The expression level of p-ERK protein in A549 and H1299 cells treated with sorafenib was lower than that in the untreated control group (P〈0.05). Conclusion: Sorafenib can inhibit the proliferation of human NSCLC A549 and H1299 cells and induce the apoptosis. This effect may be associated with the block of ERK signaling pathway.
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