PMID- 32849956
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220416
IS  - 1920-454X (Electronic)
IS  - 1920-4531 (Print)
IS  - 1920-4531 (Linking)
VI  - 11
IP  - 4
DP  - 2020 Aug
TI  - Effect of Rapamycin on the Radio-Sensitivity of Cultured Tumor Cells Following 
      Boron Neutron Capture Reaction.
PG  - 158-164
LID - 10.14740/wjon1296 [doi]
AB  - BACKGROUND: Mammalian target of rapamycin (mTOR) signaling pathway has been 
      implicated in multiple mechanisms of resistance to anticancer drugs and poor 
      treatment outcomes in various human cancers. Meanwhile, clinical boron neutron 
      capture therapy (BNCT) has been carried out for patients with malignant gliomas, 
      melanomas, inoperable head and neck tumors and oral cancers. This study aimed to 
      evaluate the effect of mTOR inhibition on radio-sensitivity of cultured tumor 
      cells in BNCT, employing p-boronophenylalanine-(10)B (BPA) as a (10)B-carrier. 
      METHODS: Cultured SAS cells had been incubated for 48 h at RPMI medium with mTOR 
      inhibitor, rapamycin at the dose of 1 microM, and then continuously incubated for 2 
      more hours at RPMI medium containing both BPA at the (10)B concentration of 10 
      ppm and rapamycin (1 microM). Subsequently, the SAS cells received reactor neutron 
      beams, and then surviving fraction and micronucleus frequency were determined. 
      RESULTS: SAS cells incubated with rapamycin showed resistance to gamma-rays compared 
      with no treatment with rapamycin. The efficiency of delivery of (10)B from BPA 
      into cultured SAS cells was reduced through combining with rapamycin, leading to 
      reduced sensitivity following boron neutron capture reaction. CONCLUSIONS: Since 
      many tumors are characterized by deregulated PI3K/AKT/mTOR pathway, rapamycin is 
      thought to inhibit the pathway and tumor growth. However, it was revealed that 
      rapamycin can also inhibit the transport of (10)B for BNCT into tumor cells. When 
      BNCT is combined with mTOR inhibitor, the efficiency as cancer treatment can be 
      reduced by repression of distributing (10)B in tumor cells, warranting precaution 
      when the two strategies are combined.
CI  - Copyright 2020, Tatebe et al.
FAU - Tatebe, Hitoshi
AU  - Tatebe H
AD  - Department of Radiation Oncology, Kindai University Faculty of Medicine, 
      Ohno-Higashi, Osaka-Sayama, Osaka, Japan.
FAU - Masunaga, Shin-Ichiro
AU  - Masunaga SI
AD  - Particle Radiation Biology, Division of Radiation Life Science, Institute for 
      Integrated Radiation and Nuclear Science, Kyoto University, Kumatori, Osaka, 
      Japan.
FAU - Nishimura, Yasumasa
AU  - Nishimura Y
AD  - Department of Radiation Oncology, Kindai University Faculty of Medicine, 
      Ohno-Higashi, Osaka-Sayama, Osaka, Japan.
LA  - eng
PT  - Journal Article
DEP - 20200810
PL  - Canada
TA  - World J Oncol
JT  - World journal of oncology
JID - 101564097
PMC - PMC7430854
OTO - NOTNLM
OT  - Boron neutron capture therapy
OT  - Boronophenylalanine-10B
OT  - Rapamycin
COIS- All authors declare that they have no conflict of interest concerning this 
      manuscript.
EDAT- 2020/08/28 06:00
MHDA- 2020/08/28 06:01
PMCR- 2020/08/10
CRDT- 2020/08/28 06:00
PHST- 2020/06/13 00:00 [received]
PHST- 2020/07/15 00:00 [accepted]
PHST- 2020/08/28 06:00 [entrez]
PHST- 2020/08/28 06:00 [pubmed]
PHST- 2020/08/28 06:01 [medline]
PHST- 2020/08/10 00:00 [pmc-release]
AID - 10.14740/wjon1296 [doi]
PST - ppublish
SO  - World J Oncol. 2020 Aug;11(4):158-164. doi: 10.14740/wjon1296. Epub 2020 Aug 10.