Activation of mTORC1 under nutrient starvation conditions increases cellular radiosensitivity in human liver cancer cell lines, HepG2 and HuH6

Yasuhiko Murata, Yoshihiko Uehara, Yoshio Hosoi

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background The presence of unperfused regions containing cells under hypoxic and nutrient starvation conditions contributes to radioresistance in solid human tumors. It is well known that the hypoxia causes cellular radioresistance. However, the effects of nutrient starvation conditions on cellular radiosensitivity remain unclear. Methods Human liver cancer cell lines, HepG2 and HuH6, and a SV40-transformed human fibroblast cell line, LM217 were used to examine the effects of nutrient starvation conditions on cellular radiosensitivity and on activity of mammalian target of rapamycin complex 1 (mTORC1) that senses cellular nutrient conditions and affects radiosensitivity. Results In contrast to suppressed mTORC1 activity under nutrient starvation conditions in LM217, HepG2 and HuH6 cells showed increased mTORC1 activity under nutrient starvation conditions. Both AMP-activated protein kinase (AMPK) and Akt were activated under nutrient starvation conditions in all the three cell lines. Under starvation conditions, increased radiosensitivity was observed in HepG2 and HuH6 cells, in contrast to decreased radiosensitivity in LM217 cells. Knockdown of mTOR using siRNA for mTOR or treatment with a mTOR inhibitor, rapamycin, suppressed the increased radiosensitivity under starvation conditions in HepG2 cells. Conclusion Our data show for the first time that nutrient starvation conditions activate mTORC1 and increase radiosensitivity through mTORC1 activation in liver cancer cell lines, HepG2 and HuH6.

Original languageEnglish
Pages (from-to)684-690
Number of pages7
JournalBiochemical and biophysical research communications
Volume468
Issue number4
DOIs
Publication statusPublished - 2015 Dec 25

Keywords

  • Liver cancer
  • Radiosensitivity
  • Rapamycin
  • Starvation
  • mTORC1

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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