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Superior Effect of the Combination of Carbon-Ion Beam Irradiation and 5-Fluorouracil on Colorectal Cancer Stem Cells in vitro and in vivo

 Woong Sub Koom  ;  Sei Sai  ;  Masao Suzuki  ;  Akira Fujimori  ;  Shigeru Yamada  ;  Hirohiko Tsujii 
 ONCOTARGETS AND THERAPY, Vol.13 : 12625-12635, 2020-12 
Journal Title
Issue Date
5-FU ; colorectal cancer stem cell ; heavy ion radiation
Background: The aim of this study was to investigate whether carbon-ion beam irradiation in combination with 5-fluorouracil (5-FU) is superior to carbon-ion beam irradiation alone in targeting colorectal cancer stem-like cells (CSCs). Materials and methods: Human colorectal cancer (CRC) cells, HCT116 and HT29, were treated with carbon-ion beam irradiation alone or in combination with 5-FU. Cell viability assay, colony and spheroid formation assay, apoptotic assay, and quantitative real-time PCR analysis of apoptosis- and autophagy-related gene expression were performed. Results: Carbon-ion beam irradiation dose-dependently decreased CRC cell viability and showed significantly enhanced cell killing effect when combined with 5-FU. Carbon-ion beam irradiation in combination with 5-FU significantly increased the percentage of apoptotic cells. The expression of some apoptotic and autophagy-related genes such as Bax, Bcl2, Beclin1 and ATG7 was significantly induced by carbon-ion beam irradiation alone and was further enhanced when the beam was combined with 5-FU. The spheroid forming capacity of CD133+ cell subpopulations was significantly inhibited by carbon-ion beam in combination with 5-FU. Histopathologically, the combination of carbon-ion beam irradiation and 5-FU destroyed more xenograft tumor cells, and resulted in increased necrosis, cavitation, and fibrosis, compared to carbon-ion beam irradiation alone. Conclusion: In conclusion, carbon-ion beam treatment combined with 5-FU has the potential to kill CRC cells including CSCs by inducing increased apoptosis and autophagy.
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1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Koom, Woong Sub(금웅섭) ORCID logo https://orcid.org/0000-0002-9435-7750
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