TY - JOUR
T1 - Enhancement of autophagy is a potential modality for tumors refractory to radiotherapy
AU - Fukumoto, M.
AU - Kuwahara, Y.
AU - Oikawa, T.
AU - Ochiai, Y.
AU - Roudkenar, M. H.
AU - Fukamoto, M.
AU - Shimura, T.
AU - Ohtake, Y.
AU - Ohkubo, Y.
AU - Mori, S.
AU - Uchiya, M. A.Y.
PY - 2011/6
Y1 - 2011/6
N2 - 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 for4>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.
AB - 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 for4>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.
KW - 3-Methyladenine
KW - Autophagy
KW - Radioresistant cells
KW - Radiotherapy
KW - Rapamycin
UR - http://www.scopus.com/inward/record.url?scp=79960007748&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79960007748&partnerID=8YFLogxK
U2 - 10.1038/cddis.2011.56
DO - 10.1038/cddis.2011.56
M3 - Article
C2 - 21716292
AN - SCOPUS:79960007748
VL - 2
JO - Cell Death and Disease
JF - Cell Death and Disease
SN - 2041-4889
IS - 6
M1 - e177
ER -