BAG3 gene silencing sensitizes leukemic cells to Bortezomib-induced apoptosis.

Abstract

Proteasome inhibition has emerged as a powerful option for the treatment of a number of malignancies including leukemias. However, Bortezomib showed limited single-agent activity for patients with leukemia. Here, we report for the first time that Bortezomib up-regulated a novel antiapoptotic protein, BAG3, in human leukemic cells. BAG3 gene knockdown with shRNA greatly potentiated the generation of apoptosis by Bortezomib in leukemia cells. Furthermore, BAG3 silencing enhanced the antitumor activity of Bortezomib dramatically in a nude mouse model. Our results indicate that knocking down BAG3 gene is a promising new approach to enhance the therapeutic potency of Bortezomib in leukemia.

• Authors: Peng Liu, Bei Xu, Jianyong Li, Hua Lu
• Journal: FEBS letters (FEBS Lett) Vol. 583 Issue 2 Pg. 401-6 (Jan 22 2009) ISSN: 1873-3468 [Electronic] England
• PMID: 19111544 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Antineoplastic Agents
• Apoptosis Regulatory Proteins
• BAG3 protein, human
• Boronic Acids
• Cysteine Proteinase Inhibitors
• Proteasome Inhibitors
• Pyrazines
• RNA, Small Interfering
• Bortezomib
• Caspase 3

Topics

• Adaptor Proteins, Signal Transducing (genetics)
• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (genetics)
• Apoptosis Regulatory Proteins
• Boronic Acids (pharmacology)
• Bortezomib
• Caspase 3 (metabolism)
• Cysteine Proteinase Inhibitors (pharmacology)
• Drug Resistance, Neoplasm (genetics)
• Gene Knockdown Techniques
• Gene Silencing
• Humans
• Leukemia (enzymology)
• Mice
• Proteasome Inhibitors
• Pyrazines (pharmacology)
• RNA, Small Interfering (genetics)