Everolimus sensitizes Ras-transformed cells to radiation in vitro through the autophagy pathway

Yu Chieh Su, Chih Chia Yu, Fei Ting Hsu, Shu Ling Fu, Jeng Jong Hwang, Ling Chien Hung, Moon Sing Lee, Wen Yen Chiou, Hon Yi Lin, Shih Kai Hung

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Modern radiation therapy strives to minimize injury to organs while increasing the anticancer effects. The present study aimed to investigate the radiosensitizing effects of everolimus and to examine the molecular mechanisms responsible for everolimus-mediated radiosensitization. Radiation in combination with everolimus (30 nM) sensitized Ras-transformed cells to radiation in vitro. Radiation induced apoptotic markers (sub-G1 cell accumulation, membrane inversion and DNA fragmentation) and treatment with everolimus did not promote radiation-induced apoptosis. However, LC3-II expression increased following combination treatment with everolimus and radiation, and the radiosensitizing effects of everolimus were reversed following transfection with small interfering RNA (siRNA) targeting Beclin 1. In addition, the protein levels of activated S6 kinase 1 (S6K1) were significantly reduced following treatment with everolimus, and the phosphorylation of factor 4E binding protein 1 (4EBP1) was suppressed following combination treatment. Taken together, our data demonstrate that everolimus sensitizes Ras-transformed cells to radiation in vitro. Everolimus-mediated radiosensitization is associated with the autophagy pathway. Thus, everolimus is a novel radiosensitizing agent with potential for use in cancer radiotherapy.

Original languageEnglish
Pages (from-to)1417-1422
Number of pages6
JournalInternational Journal of Molecular Medicine
Volume34
Issue number5
DOIs
Publication statusPublished - Nov 1 2014
Externally publishedYes

Keywords

  • Autophagy
  • Everolimus
  • Radiosensitization
  • Ras

ASJC Scopus subject areas

  • Genetics
  • Medicine(all)

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