TY - JOUR
T1 - Novel application of radotinib for the treatment of solid tumors via natural killer cell activation
AU - Kim, Kyung Eun
AU - Park, Sunyoung
AU - Cheon, Soyoung
AU - Kim, Dong Yeon
AU - Cho, Dae Jin
AU - Park, Jeong Min
AU - Hur, Dae Young
AU - Park, Hyun Jeong
AU - Cho, Daeho
N1 - Funding Information:
This work was supported by the Ministry of Knowledge Economy (Grant no. 10033778) and Creative Materials Discovery Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (2016M3D1A1021387).
Publisher Copyright:
Copyright © 2018 Kyung Eun Kim et al.
PY - 2018
Y1 - 2018
N2 - Radotinib (SupectTM) 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.
AB - Radotinib (SupectTM) 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.
UR - http://www.scopus.com/inward/record.url?scp=85060632929&partnerID=8YFLogxK
U2 - 10.1155/2018/9580561
DO - 10.1155/2018/9580561
M3 - Article
C2 - 30687767
AN - SCOPUS:85060632929
SN - 2314-8861
VL - 2018
JO - Journal of Immunology Research
JF - Journal of Immunology Research
M1 - 9580561
ER -