BIIB021, a novel Hsp90 inhibitor, sensitizes esophageal squamous cell carcinoma to radiation.

Abstract

BIIB021 is a novel, orally available inhibitor of heat shock protein 90 (Hsp90) that is currently in phase I/II clinical trials. BIIB021 induces the apoptosis of various types of tumor cells in vitro and in vivo. The aim of this study is to investigate the effect of BIIB021 on the radiosensitivity of esophageal squamous cell carcinoma (ESCC). The results indicated that BIIB021 exhibited strong antitumor activity in ESCC cell lines, either as a single agent or in combination with radiation. BIIB021 significantly downregulated radioresistant proteins including EGFR, Akt, Raf-1 of ESCC cell lines, increased apoptotic cells and enhanced G2 arrest that is more radiosensitive cell cycle phase. These results suggest that this synthetic Hsp90 inhibitor simultaneously affects multiple pathways involved in tumor development and progression in the ESCC setting and may represent a better strategy for the treatment of ESCC patients, either as a monotherapy or a radiosensitizer.

• Authors: Xin-Tong Wang, Ci-Hang Bao, Yi-Bin Jia, Nana Wang, Wei Ma, Fang Liu, Cong Wang, Jian-Bo Wang, Qing-Xu Song, Yu-Feng Cheng
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 452 Issue 4 Pg. 945-50 (Oct 03 2014) ISSN: 1090-2104 [Electronic] United States
• PMID: 25223594 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• 6-chloro-9-(4-methoxy-3,5-dimethylpyridin-2-ylmethyl)-9H-purin-2-ylamine
• HSP90 Heat-Shock Proteins
• Neoplasm Proteins
• Pyridines
• Radiation-Sensitizing Agents
• Adenine

Topics

• Adenine (analogs & derivatives)
• Apoptosis (radiation effects)
• Carcinoma, Squamous Cell (metabolism, pathology)
• Cell Line, Tumor
• Esophageal Neoplasms (metabolism, pathology)
• G2 Phase Cell Cycle Checkpoints (radiation effects)
• HSP90 Heat-Shock Proteins (antagonists & inhibitors)
• Humans
• Neoplasm Proteins (metabolism)
• Pyridines
• Radiation Tolerance (drug effects)
• Radiation-Sensitizing Agents (pharmacology)