期刊
WORLD JOURNAL OF GASTROENTEROLOGY
卷 17, 期 2, 页码 181-190出版社
BAISHIDENG PUBLISHING GROUP INC
DOI: 10.3748/wjg.v17.i2.181
关键词
Gastric cancer; Oxaliplatin; Phosphatidylinositol 3 '-kinase/Akt pathway; Death receptor pathway; Apoptosis; LY294002
资金
- National Natural Science Foundation of China [30470782]
AIM: To examine the effects of combined treatment of oxaliplatin and phosphatidylinositol 3'-kinase inhibitor, 2-(4-morpholinyl)-8-phenyl-4H-1-benzoPyran-4-one (LY294002) for gastric cancer. METHODS: Cell viability was evaluated by 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide assay. Apoptotic cells were detected by flow cytometric analysis and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Western blotting and immuno-precipitation were used to examine protein expression and recruitment, respectively. Nuclear factor kappa B (NF kappa B) binding activities were investigated using electrophoretic mobility shift assay. Nude mice were used to investigate tumor growth. RESULTS: Treatment with combined oxaliplatin and LY294002 resulted in increased cell growth inhibition and cell apoptosis in vitro, and increased tumor growth inhibition and cell death in the tumor mass in vivo. In MKN45 and AGS cells, oxaliplatin treatment promoted both protein kinase B (Akt) and NF kappa B activation, while pretreatment with LY294002 significantly attenuated oxaliplatin-induced Akt activity and NF kappa B binding. LY294002 promoted oxaliplatin-induced Fas ligand (FasL) expression, Fas-associated death domain protein recruitment, caspase-8, Bid, and caspase-3 activation, and the short form of cellular caspase-8/FLICEinhibitory protein (c-FLIPs) inhibition. In vivo, LY294002 inhibited oxaliplatin-induced activation of Akt and NF kappa B, and increased oxaliplatin-induced expression of FasL, inhibition of c-FLIPs, and activation of caspase-8, Bid, and caspase-3. CONCLUSION: Combination of oxaliplatin and LY294002 was therapeutically promising for gastric cancer treatment. The enhanced sensitivity of the combined treatment was associated with the activation of the death receptor pathway. (C) 2011 Baishideng. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据