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Bortezomib synergizes TRAIL-induced apoptosis in gastric cancer cells.
MedLine Citation:
PMID:  20393880     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Background/Aims Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as a newly identified biological agent has shown promising antitumor effects in a wide range of cancers. However, gastric cancer cells are less sensitive than other cancer cells to TRAIL-induced apoptosis.Here, we combined TRAIL with bortezomib, a proteasomal inhibitor to induce apoptosis in three gastric cancer cell lines.Methods After the cells were treated with TRAIL and/or bortezomib, the cell viability, apoptosis and cell cycle distribution were examined. The levels of death receptors and the mitochondrial membrane potential were also detected. The expression of apoptosis-associated proteins was determined by Western blot.Results Bortezomib at low concentration significantly(P<0.05) enhanced the cytotoxic effect of TRAIL by enhancing apoptosis as well as cell cycle arrest at G2/M phase. The enhancement of efficiency of TRAIL by bortezomib involved up-regulation of death receptor 4 and 5, as well as reduction of the mitochondrial membrane potential. Further study showed that combined treatment with TRAIL and bortezomib down-regulated anti-apoptotic protein cIAP-1, and over expression of cIAP-1 significantly(P\0.05) reduced the synergistic effect between TRAIL and bortezomib.Conclusions Bortezomib synergizes TRAIL-induced apoptosis in human gastric cancer cells. The synergistic effect between these two drugs is associated with up-regulation of death receptors and down-regulation of cIAP-1.The combination of TRAIL and bortezomib might be an effective regimen for the treatment of advanced gastric cancer.
Authors:
Jing Liu; Xiu-Juan Qu; Ling Xu; Ye Zang; Jing-Lei Qu; Ke-Zuo Hou; Yun-Peng Liu
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Digestive diseases and sciences     Volume:  55     ISSN:  1573-2568     ISO Abbreviation:  Dig. Dis. Sci.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7902782     Medline TA:  Dig Dis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3361-8     Citation Subset:  AIM; IM    
Affiliation:
Department of Medical Oncology, The First Hospital of China Medical University, 110001 Shenyang, People’s Republic of China. liujing_cmu@hotmail.com
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