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

Highlights: • BIIB021 downregulated radioresistant proteins in ESCC cell lines. • BIIB021 increased radiation-induced apoptotic cells. • BIIB021 enhanced G{sub 2} arrest in ESCC cell lines. • BIIB021 is a good candidate for radiosensitizer in radiotherapy of ESCC patients. - 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 G{sub 2} 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:
; ; ;  [1] ;  [2] ;  [3] ; ; ;  [1] ;  [1]
  1. Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012 (China)
  2. Department of Radiation Oncology, Cancer Hospital, General Hospital of Ningxia Medical University, Yinchuan 750000 (China)
  3. Medical Imaging, Shandong Medical College, Jinan 250002 (China)
Publication Date:
OSTI Identifier:
22416767
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 452; Journal Issue: 4; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CARCINOMAS; CELL CYCLE; CLINICAL TRIALS; ESOPHAGUS; HEAT-SHOCK PROTEINS; IN VITRO; IN VIVO; PATIENTS; RADIOSENSITIVITY; RADIOTHERAPY; TUMOR CELLS