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Novel Application of Radotinib for the Treatment of Solid Tumors via Natural Killer Cell Activation
Radotinib (Supect™) was developed to treat chronic myeloid leukemia (CML) as a BCR-ABL1 tyrosine kinase inhibitor (TKI). Other TKIs, including imatinib and nilotinib, were also developed for treatment of CML, and recent studies were increasing about the therapeutic effects of other TKIs on solid tum...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330826/ https://www.ncbi.nlm.nih.gov/pubmed/30687767 http://dx.doi.org/10.1155/2018/9580561 |
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author | Kim, Kyung Eun Park, Sunyoung Cheon, Soyoung Kim, Dong Yeon Cho, Dae Jin Park, Jeong Min Hur, Dae Young Park, Hyun Jeong Cho, Daeho |
author_facet | Kim, Kyung Eun Park, Sunyoung Cheon, Soyoung Kim, Dong Yeon Cho, Dae Jin Park, Jeong Min Hur, Dae Young Park, Hyun Jeong Cho, Daeho |
author_sort | Kim, Kyung Eun |
collection | PubMed |
description | Radotinib (Supect™) was developed to treat chronic myeloid leukemia (CML) as a BCR-ABL1 tyrosine kinase inhibitor (TKI). Other TKIs, including imatinib and nilotinib, were also developed for treatment of CML, and recent studies were increasing about the therapeutic effects of other TKIs on solid tumors. However, the effect of radotinib on solid tumors has not yet been investigated. In this study, radotinib killed CML cell line K562 directly; however, radotinib did not enhance NK cell cytotoxicity against K562 cells. Because K562 is known as a Fas-negative cell line, we investigated whether radotinib could regulate cell cytotoxicity against various Fas-expressing solid cancer cell lines. Radotinib dramatically increased NK cell cytotoxicity against various Fas-expressing solid cancer cells, including lung, breast, and melanoma cells. Additionally, the efficiency of radotinib-enhanced cytotoxicity was lower in Fas siRNA-transfected cells than in negative controls, suggesting that Fas signaling might be involved in the radotinib-enhanced NK cell cytotoxicity. This study provides the first evidence that radotinib could be used as an effective and strong therapeutic to treat solid tumors via upregulation of NK cell cytotoxicity, suggesting that radotinib has indirect killing mechanisms via upregulation of antitumor innate immune responses as well as direct killing activities for CML cells. |
format | Online Article Text |
id | pubmed-6330826 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-63308262019-01-27 Novel Application of Radotinib for the Treatment of Solid Tumors via Natural Killer Cell Activation Kim, Kyung Eun Park, Sunyoung Cheon, Soyoung Kim, Dong Yeon Cho, Dae Jin Park, Jeong Min Hur, Dae Young Park, Hyun Jeong Cho, Daeho J Immunol Res Research Article Radotinib (Supect™) was developed to treat chronic myeloid leukemia (CML) as a BCR-ABL1 tyrosine kinase inhibitor (TKI). Other TKIs, including imatinib and nilotinib, were also developed for treatment of CML, and recent studies were increasing about the therapeutic effects of other TKIs on solid tumors. However, the effect of radotinib on solid tumors has not yet been investigated. In this study, radotinib killed CML cell line K562 directly; however, radotinib did not enhance NK cell cytotoxicity against K562 cells. Because K562 is known as a Fas-negative cell line, we investigated whether radotinib could regulate cell cytotoxicity against various Fas-expressing solid cancer cell lines. Radotinib dramatically increased NK cell cytotoxicity against various Fas-expressing solid cancer cells, including lung, breast, and melanoma cells. Additionally, the efficiency of radotinib-enhanced cytotoxicity was lower in Fas siRNA-transfected cells than in negative controls, suggesting that Fas signaling might be involved in the radotinib-enhanced NK cell cytotoxicity. This study provides the first evidence that radotinib could be used as an effective and strong therapeutic to treat solid tumors via upregulation of NK cell cytotoxicity, suggesting that radotinib has indirect killing mechanisms via upregulation of antitumor innate immune responses as well as direct killing activities for CML cells. Hindawi 2018-12-31 /pmc/articles/PMC6330826/ /pubmed/30687767 http://dx.doi.org/10.1155/2018/9580561 Text en Copyright © 2018 Kyung Eun Kim et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Kim, Kyung Eun Park, Sunyoung Cheon, Soyoung Kim, Dong Yeon Cho, Dae Jin Park, Jeong Min Hur, Dae Young Park, Hyun Jeong Cho, Daeho Novel Application of Radotinib for the Treatment of Solid Tumors via Natural Killer Cell Activation |
title | Novel Application of Radotinib for the Treatment of Solid Tumors via Natural Killer Cell Activation |
title_full | Novel Application of Radotinib for the Treatment of Solid Tumors via Natural Killer Cell Activation |
title_fullStr | Novel Application of Radotinib for the Treatment of Solid Tumors via Natural Killer Cell Activation |
title_full_unstemmed | Novel Application of Radotinib for the Treatment of Solid Tumors via Natural Killer Cell Activation |
title_short | Novel Application of Radotinib for the Treatment of Solid Tumors via Natural Killer Cell Activation |
title_sort | novel application of radotinib for the treatment of solid tumors via natural killer cell activation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330826/ https://www.ncbi.nlm.nih.gov/pubmed/30687767 http://dx.doi.org/10.1155/2018/9580561 |
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