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Chemoresistance to 5-FU inhibited by 635 nm LED irradiation in CD133+ KB cell line

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Abstract

Consistent with cancer stem cell theory, a small fraction of cancer cells, described as cancer stem cells (CSCs), may promote tumor recurrence and anti-cancer drug resistance. Therefore, much effort has been devoted to the development of CSC targeted therapy to vanquish drug resistance. In this study, we have investigated the effect of multiple light-emitting diode (LED) irradiation treatments with conventional anti-cancer drugs on CSC-like oral cancer cells that acquired stemness by ectopic over expression of CD133. To evaluate combined LED irradiation anti-cancer drug effects, we investigated the chemosensitizing effect of 635 nm irradiation on 5-fluorouracil (5FU)-treated KBCD133+ and KBVec cells, interrogating the underlying molecular mechanisms associated with stemness and apoptosis that are responsible for chemopreventive activity. In addition, combination therapy with LED irradiation and 5-FU treatment was carried out in KBCD133+ and KBVec cell-inoculated mouse models. LED irradiation of 635 nm inhibited CSC-like properties consistent with a decrease in OCT4 and NANOG protein expression, reducing colony-forming ability. In addition, LED irradiation enhanced 5-FU-induced cytotoxicity and improved 5-FU chemosensitivity in KBCD133+ via enhancement of apoptosis. These findings were validated in vivo, wherein LED irradiation combined with 5-FU treatment inhibited tumor growth in KBCD133+-inoculated mice. Collectively, our results provide novel evidence for 635 nm irradiation-induced 5-FU chemosensitization of CSC in oral cancer. In addition, this research highlights that 635 nm LED irradiation may serve as an adjunct treatment to conventional chemotherapeutic drugs in patients with oral cancer.

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Author contributions

D. Kim, M. Park, H. Jang, H. Hyun, and W. Lim performed the experiments. D. Kim, M. Park, and W. Lim reviewed, analyzed, and interpreted the data. D. Kim, M. Park, and W. Lim wrote the paper. All authors discussed the results and commented on the manuscript.

Funding information

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (Grant No. 2016R1D1A3B03934601), the Ministry of Trade, Industry & Energy (MOTIE), Korea Institute for Advancement of Technology (KIAT) through the Encouragement Program for The Industries of Economic Cooperation Region (Grant No. R0004732), and by a grant from the Clinical Medicine Research Institute of the Chosun University Hospital (2014).

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Author notes

  1. Donghwi Kim and Mineon Park contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopedic Surgery, Chosun University Hospital, Gwangju, 61453, South Korea

    Donghwi Kim, Mineon Park, Hyunwoong Jang & Wonbong Lim

  2. Laboratory of Orthopedic Research, Chosun University Hospital, Gwangju, 61453, South Korea

    Donghwi Kim, Mineon Park & Wonbong Lim

  3. Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, 61469, South Korea

    Hoon Hyun

  4. Department of Premedical Program, School of Medicine, Chosun University, Gwangju, 61452, South Korea

    Wonbong Lim

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  1. Donghwi Kim
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  2. Mineon Park
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Correspondence to Wonbong Lim.

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Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards approved by the Institutional Animal Care and Use Committee, Chosun University, Gwangju, Korea (CIACUC2016-S0007). This article does not contain any studies with human participants performed by any of the authors.

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The authors declare that they have no conflict of interest.

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Kim, D., Park, M., Jang, H. et al. Chemoresistance to 5-FU inhibited by 635 nm LED irradiation in CD133+ KB cell line. Lasers Med Sci 33, 57–66 (2018). https://doi.org/10.1007/s10103-017-2335-2

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  • DOI: https://doi.org/10.1007/s10103-017-2335-2

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