Effect of Rapamycin on the Radio-Sensitivity of Cultured Tumor Cells Following Boron Neutron Capture Reaction.
World J Oncol
; 11(4): 158-164, 2020 Aug.
Article
en En
| MEDLINE
| ID: mdl-32849956
ABSTRACT
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-10B (BPA) as a 10B-carrier.METHODS:
Cultured SAS cells had been incubated for 48 h at RPMI medium with mTOR inhibitor, rapamycin at the dose of 1 µM, and then continuously incubated for 2 more hours at RPMI medium containing both BPA at the 10B concentration of 10 ppm and rapamycin (1 µM). 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 γ-rays compared with no treatment with rapamycin. The efficiency of delivery of 10B 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 10B for BNCT into tumor cells. When BNCT is combined with mTOR inhibitor, the efficiency as cancer treatment can be reduced by repression of distributing 10B in tumor cells, warranting precaution when the two strategies are combined.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Tipo de estudio:
Diagnostic_studies
Idioma:
En
Revista:
World J Oncol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Japón