期刊
RADIOTHERAPY AND ONCOLOGY
卷 150, 期 -, 页码 253-261出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.radonc.2020.07.034
关键词
Cancer stem cell; Chondrosarcoma; Particle therapy; mTOR inhibitor; miR-34
资金
- Transverse Division no4 (Radiobiology) of the French Alternative Energies and Atomic Energy Commission
- Okinawa Institute of Science and Technology Graduate University (OIST)
- JSPS-MAEDI France-Japan [PHC 35973SB, JSPS 16031011-000323]
- ANR (Equipex Rec-Hadron) [ANR-10-EQPX-1401]
- ANR (Investissement d'Avenir France Hadron ) [11-INBS-0007]
- Ligue contre le Cancer, comites de Normandie (comite de l'Orne)
- JSPS Kakenhi [K1907765]
- [15J104]
Background and purpose: High-grade chondrosarcomas are chemoand radio-resistant cartilage-forming tumors of bone that often relapse and metastase. Thus, new therapeutic strategies are urgently needed. Material and methods: Chondrosarcoma cells (CH-2879) were exposed to carbon-ion irradiation, combined with miR-34 mimic and/or rapamycin administration. The effects of treatment on cancer stem cells, stemness-associated phenotype, radioresistance and tumor-initiating properties were evaluated. Results: We show that high-grade chondrosarcoma cells contain a population of radioresistant cancer stem cells that can be targeted by a combination of carbon-ion therapy, miR-34 mimic administration and/or rapamycin treatment that triggers FOXO3 and miR-34 over-expression. mTOR inhibition by rapamycin triggered FOXO3 and miR-34, leading to KLF4 repression. Conclusion: Our results show that particle therapy combined with molecular treatments effectively controls cancer stem cells and may overcome treatment resistance of high-grade chondrosarcoma. (C) 2020 Elsevier B.V. All rights reserved.
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