title: Enhancement of autophagy is a potential modality for tumors refractory to radiotherapy.
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.
authors.affiliation: Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kuwahara
authors.forename: T
authors.initials: T
authors.lastname: Oikawa
authors.forename: Y
authors.initials: Y
authors.lastname: Ochiai
authors.forename: M H
authors.initials: MH
authors.lastname: Roudkenar
authors.forename: M
authors.initials: M
authors.lastname: Fukumoto
authors.forename: T
authors.initials: T
authors.lastname: Shimura
authors.forename: Y
authors.initials: Y
authors.lastname: Ohtake
authors.forename: Y
authors.initials: Y
authors.lastname: Ohkubo
authors.forename: S
authors.initials: S
authors.lastname: Mori
authors.forename: Y
authors.initials: Y
authors.lastname: Uchiyama
authors.forename: M
authors.initials: M
authors.lastname: Fukumoto
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D001343:Autophagy / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D011836:Radiation Tolerance / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D014965:X-Rays
chemical_list: C025946:3-methyladenine; D000225:Adenine