Bortezomib synergizes TRAIL-induced apoptosis in gastric cancer cells.

Abstract

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
• Journal: Digestive diseases and sciences (Dig Dis Sci) Vol. 55 Issue 12 Pg. 3361-8 (Dec 2010) ISSN: 1573-2568 [Electronic] United States
• PMID: 20393880 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Boronic Acids
• Pyrazines
• TNF-Related Apoptosis-Inducing Ligand
• TNFSF10 protein, human
• Bortezomib

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Boronic Acids (pharmacology)
• Bortezomib
• Cell Line, Tumor
• Cell Survival (drug effects)
• Drug Synergism
• Humans
• Pyrazines (pharmacology)
• Stomach Neoplasms (drug therapy)
• TNF-Related Apoptosis-Inducing Ligand (pharmacology)