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Carbon-Ion Beam Irradiation and the miR-200c Mimic Effectively Eradicate Pancreatic Cancer Stem Cells Under in vitro and in vivo Conditions

Authors
 Sei Sai  ;  Eun Ho Kim  ;  Woong Sub Koom  ;  Guillaume Vares  ;  Masao Suzuki  ;  Shigeru Yamada  ;  Mitsuhiro Hayashi 
Citation
 ONCOTARGETS AND THERAPY, Vol.14 : 4749-4760, 2021-09 
Journal Title
ONCOTARGETS AND THERAPY
Issue Date
2021-09
Keywords
carbon-ion beam ; miR-200c ; pancreatic cancer stem cell
Abstract
Purpose: The study investigated the molecular mechanisms that killed pancreatic cancer cells, including cancer stem cells (CSCs), by carbon ion beam irradiation alone or in combination with miRNA-200c under in vitro and in vivo conditions.

Methods: Human pancreatic cancer (PC) cells, PANC1 and PK45, were treated with carbon-ion beam irradiation alone or in combination with microRNA-200c (miR-200c) mimic. Cell viability assay, colony and spheroid formation assay, quantitative real-time PCR analysis of apoptosis-, autophagy-, and angiogenesis-related gene expression, xenograft tumor control and histopathological analyses were performed.

Results: The cell viability assay showed that transfection of the miRNA-200c (10 nM) mimic into pancreatic CSC (CD44+/ESA+) and non-CSC (CD44-/ESA-) significantly suppressed proliferation of both types of cell populations described above. Combining carbon-ion beam irradiation with the miRNA-200c mimic significantly reduced the colony as well as spheroid formation abilities compared to that observed with the treatment of carbon-ion beam alone or X-ray irradiation combined with the miRNA-200c mimic. Moreover, the combination of carbon ion beam irradiation and miRNA-200c mimic increased the expression of apoptosis-related gene BAX, autophagy-related genes Beclin-1 and p62, addition of gemcitabine (GEM) further enhanced the expression of these genes. In vivo data showed that carbon-ion beam irradiation in combination with the miRNA-200c mimic effectively suppressed xenograft tumor growth and significantly induced tumor necrosis and cavitation.

Conclusion: The combination of miRNA-200c mimic and carbon ion beam irradiation may be powerful radiotherapy that significantly kills pancreatic cancer cells containing CSCs and enhances the effect of carbon-ion beam irradiation compared to carbon-ion beam irradiation alone.
Files in This Item:
T202105025.pdf Download
DOI
10.2147/OTT.S311567
Appears in Collections:
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
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/187087
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