| Bortezomib synergizes TRAIL-induced apoptosis in gastric cancer cells. | |
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MedLine Citation:
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PMID: 20393880 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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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. |
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Authors:
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Jing Liu; Xiu-Juan Qu; Ling Xu; Ye Zang; Jing-Lei Qu; Ke-Zuo Hou; Yun-Peng Liu |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Digestive diseases and sciences Volume: 55 ISSN: 1573-2568 ISO Abbreviation: Dig. Dis. Sci. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-21 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7902782 Medline TA: Dig Dis Sci Country: United States |
Other Details:
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Languages: eng Pagination: 3361-8 Citation Subset: AIM; IM |
Affiliation:
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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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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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