Enhancement of autophagy is a potential modality for tumors refractory to radiotherapy

M. Fukumoto, Y. Kuwahara, T. Oikawa, Y. Ochiai, M. H. Roudkenar, M. Fukamoto, T. Shimura, Y. Ohtake, Y. Ohkubo, S. Mori, M. A.Y. Uchiya

研究成果: Article査読

65 被引用数 (Scopus)

抄録

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.

本文言語English
論文番号e177
ジャーナルCell Death and Disease
2
6
DOI
出版ステータスPublished - 2011 6

ASJC Scopus subject areas

  • 免疫学
  • 細胞および分子神経科学
  • 細胞生物学
  • 癌研究

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