1. A multimodal treatment of carbon ions irradiation, miRNA-34 and mTOR inhibitor specifically control high-grade chondrosarcoma cancer stem cells.
- Author
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Vares, Guillaume, Ahire, Vidhula, Sunada, Shigeaki, Ho Kim, Eun, Sai, Sei, Chevalier, François, Romeo, Paul-Henri, Yamamoto, Tadashi, Nakajima, Tetsuo, and Saintigny, Yannick
- Subjects
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CANCER stem cells , *MTOR inhibitors , *COMBINED modality therapy , *RAPAMYCIN , *STEM cell treatment , *TREATMENT effectiveness - Abstract
• Chondrosarcoma stem cells (ChSCs) are radioresistant and are suppressed by miR-34. • mTOR inhibition by Rapamycin targets ChSCs via FOXO3 and miR-34. • Combination of carbon-ion therapy with mTOR inhibitors effectively controls ChSCs. High-grade chondrosarcomas are chemo- and radio-resistant cartilage-forming tumors of bone that often relapse and metastase. Thus, new therapeutic strategies are urgently needed. 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. 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. Our results show that particle therapy combined with molecular treatments effectively controls cancer stem cells and may overcome treatment resistance of high-grade chondrosarcoma. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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