PMID- 28718972
OWN - NLM
STAT- MEDLINE
DCOM- 20171005
LR  - 20211204
IS  - 1349-7006 (Electronic)
IS  - 1347-9032 (Print)
IS  - 1347-9032 (Linking)
VI  - 108
IP  - 10
DP  - 2017 Oct
TI  - Enhancement of mTOR signaling contributes to acquired X-ray and C-ion resistance 
      in mouse squamous carcinoma cell line.
PG  - 2004-2010
LID - 10.1111/cas.13323 [doi]
AB  - Our aim was to evaluate whether repetition of C-ion (carbon ion beam) irradiation 
      induces radioresistance as well as repeated X-ray irradiation in cancer cell 
      lines, and to find the key molecular pathway for radioresistance by comparing 
      radioresistant cancer cells with their parental cells. A mouse squamous cell 
      carcinoma cell line, NR-S1, and radioresistant cancer cells, NR-S1-C30 (C30) and 
      NR-S1-X60 (X60), established by repetition of C-ion and X-ray irradiation, 
      respectively, were used. X-ray and C-ion sensitivity, changes in lysosome, 
      mitochondria, intracellular ATP and reactive oxygen species (ROS) level, and 
      mechanistic target of rapamycin (mTOR) signaling were evaluated. Moreover, the 
      effect of rapamycin on radioresistance was also assessed. X-ray and C-ion 
      resistance of C30 cells was moderate, and the resistance of X60 cells was the 
      highest in this study. In X60 cells, the amount of lysosome, mitochondria, 
      intracellular ATP and ROS level were significantly increased, and mTOR and p70S6K 
      (ribosomal protein S6 kinase p70) phosphorylation were enhanced compared with C30 
      and NR-S1 cells. The inhibition of mTOR signaling was effective for X-ray and 
      C-ion radiosensitization in both cell lines, especially in X60 cells in which 
      X-ray and C-ion resistance was decreased to the same level as that in NR-S1 
      cells. Our results indicated that the contribution to generate X-ray and C-ion 
      resistance was less for repeated C-ion irradiations compared with repeated X-ray 
      irradiation. Moreover, we found that activated mTOR signaling contributes to 
      X-ray and C-ion resistance in the X60 cancer cells.
CI  - (c) 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd 
      on behalf of Japanese Cancer Association.
FAU - Sato, Katsutoshi
AU  - Sato K
AUID- ORCID: 0000-0001-9666-9742
AD  - Cancer Metastasis Research Team, Advanced Radiation Biology Research Program, 
      Research Center for Charged Particle Therapy, National Institute of Radiological 
      Sciences, Chiba, Japan.
AD  - Clinical Genetic Oncology, Cancer Institute Hospital, Japanese Foundation for 
      Cancer Research, Tokyo, Japan.
FAU - Azuma, Rikako
AU  - Azuma R
AD  - Cancer Metastasis Research Team, Advanced Radiation Biology Research Program, 
      Research Center for Charged Particle Therapy, National Institute of Radiological 
      Sciences, Chiba, Japan.
AD  - Department of Biomolecular Science, Graduate School of Science, Toho University, 
      Chiba.
FAU - Imai, Takashi
AU  - Imai T
AD  - National Institute of Radiological Sciences, National Institutes for Quantum and 
      Radiological Science and Technology, Chiba, Japan.
FAU - Shimokawa, Takashi
AU  - Shimokawa T
AD  - Cancer Metastasis Research Team, Advanced Radiation Biology Research Program, 
      Research Center for Charged Particle Therapy, National Institute of Radiological 
      Sciences, Chiba, Japan.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20170909
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (Reactive Oxygen Species)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Carcinoma, Squamous Cell/drug therapy/*metabolism/radiotherapy
MH  - Cell Line, Tumor
MH  - Heavy Ion Radiotherapy
MH  - Mice
MH  - Mitochondria/metabolism/radiation effects
MH  - Phosphorylation/radiation effects
MH  - *Radiation Tolerance
MH  - Reactive Oxygen Species/*metabolism
MH  - Signal Transduction
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - X-Ray Therapy
MH  - Xenograft Model Antitumor Assays
PMC - PMC5623753
OTO - NOTNLM
OT  - Acquired radioresistance
OT  - energy metabolism
OT  - mTOR signaling
OT  - rapamycin
OT  - repeated X-ray and C-ion irradiations
EDAT- 2017/07/19 06:00
MHDA- 2017/10/06 06:00
PMCR- 2017/10/01
CRDT- 2017/07/19 06:00
PHST- 2017/03/16 00:00 [received]
PHST- 2017/07/11 00:00 [revised]
PHST- 2017/07/13 00:00 [accepted]
PHST- 2017/07/19 06:00 [pubmed]
PHST- 2017/10/06 06:00 [medline]
PHST- 2017/07/19 06:00 [entrez]
PHST- 2017/10/01 00:00 [pmc-release]
AID - CAS13323 [pii]
AID - 10.1111/cas.13323 [doi]
PST - ppublish
SO  - Cancer Sci. 2017 Oct;108(10):2004-2010. doi: 10.1111/cas.13323. Epub 2017 Sep 9.