Enhancement of autophagy is a potential modality for tumors refractory to radiotherapy.
Cell Death Dis
; 2: e177, 2011 Jun 30.
Article
in En
| MEDLINE
| ID: mdl-21716292
ABSTRACT
Radiotherapy is a well-established treatment for cancer. However, the existence of radioresistant cells is one of the major obstacles in radiotherapy. In order to understand the mechanism of cellular radioresistance and develop more effective radiotherapy, we have established clinically relevant radioresistant (CRR) cell lines, which continue to proliferate under daily exposure to 2 Gray (Gy) of X-rays for >30 days. X-ray irradiation significantly induced autophagic cells in parental cells, which was exiguous in CRR cells, suggesting that autophagic cell death is involved in cellular radiosensitivity. An autophagy inducer, rapamycin sensitized CRR cells to the level of parental cells and suppressed cell growth. An autophagy inhibitor, 3-methyladenine induced radioresistance of parental cells. Furthermore, inhibition of autophagy by knockdown of Beclin-1 made parental cells radioresistant to acute radiation. These suggest that the suppression of autophagic cell death but not apoptosis is mainly involved in cellular radioresistance. Therefore, the enhancement of autophagy may have a considerable impact on the treatment of radioresistant tumor.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Radiation Tolerance
/
Autophagy
/
Neoplasms
Limits:
Humans
Language:
En
Journal:
Cell Death Dis
Year:
2011
Document type:
Article
Affiliation country:
Japan