碳离子辐射、miRNA-34和mTOR抑制剂的多模态治疗可特异性控制高级别软骨肉瘤癌干细胞。

A multimodal treatment of carbon ions irradiation, miRNA-34 and mTOR inhibitor specifically control high-grade chondrosarcoma cancer stem cells.

作者信息

Vares Guillaume, Ahire Vidhula, Sunada Shigeaki, Ho Kim Eun, Sai Sei, Chevalier François, Romeo Paul-Henri, Yamamoto Tadashi, Nakajima Tetsuo, Saintigny Yannick

机构信息

Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University (OIST), Japan.

Research Laboratory and Open Facility for Radiation Biology with Accelerated Ions (LARIA), CEA/DRF/IBFJ/IRCM, Caen, France; Centre de Recherche sur les Ions, les Matériaux et la Photonique (CIMAP), Normandie Univ/ENSICAEN/UNICAEN/CEA/CNRS, Caen, France.

出版信息

Radiother Oncol. 2020 Sep;150:253-261. doi: 10.1016/j.radonc.2020.07.034. Epub 2020 Jul 24.

DOI:10.1016/j.radonc.2020.07.034

PMID:32717360

Abstract

BACKGROUND AND PURPOSE

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.

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.

摘要