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Different Mechanisms of Action of Regorafenib and Lenvatinib on Toll-Like Receptor-Signaling Pathways in Human Hepatoma Cell Lines

Multiple kinase inhibitors are available for patients with advanced hepatocellular carcinoma (HCC). It is largely unknown whether regorafenib or lenvatinib modulates innate immunity including Toll-like receptor (TLR)-signaling pathways in HCC. We performed real-time RT-PCR to investigate 84 TLR-asso...

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Autores principales: Sasaki, Reina, Kanda, Tatsuo, Fujisawa, Mariko, Matsumoto, Naoki, Masuzaki, Ryota, Ogawa, Masahiro, Matsuoka, Shunichi, Kuroda, Kazumichi, Moriyama, Mitsuhiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246870/
https://www.ncbi.nlm.nih.gov/pubmed/32397371
http://dx.doi.org/10.3390/ijms21093349
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author Sasaki, Reina
Kanda, Tatsuo
Fujisawa, Mariko
Matsumoto, Naoki
Masuzaki, Ryota
Ogawa, Masahiro
Matsuoka, Shunichi
Kuroda, Kazumichi
Moriyama, Mitsuhiko
author_facet Sasaki, Reina
Kanda, Tatsuo
Fujisawa, Mariko
Matsumoto, Naoki
Masuzaki, Ryota
Ogawa, Masahiro
Matsuoka, Shunichi
Kuroda, Kazumichi
Moriyama, Mitsuhiko
author_sort Sasaki, Reina
collection PubMed
description Multiple kinase inhibitors are available for patients with advanced hepatocellular carcinoma (HCC). It is largely unknown whether regorafenib or lenvatinib modulates innate immunity including Toll-like receptor (TLR)-signaling pathways in HCC. We performed real-time RT-PCR to investigate 84 TLR-associated gene expression levels and compared these gene expression levels in each hepatoma cells treated with or without regorafenib or lenvatinib. In response to regorafenib, nine and 10 genes were upregulated in Huh7 and HepG2 cells, respectively, and only C-X-C motif chemokine ligand 10 was upregulated in both cell lines. A total of 14 and 12 genes were downregulated in Huh7 and HepG2 cells, respectively, and two genes (Fos proto-oncogene, AP-1 transcription factor subunit, and ubiquitin conjugating enzyme E2 N) were downregulated in both cell lines. In response to lenvatinib, four and 16 genes were upregulated in Huh7 and HepG2 cells, respectively, and two genes (interleukin 1 alpha and TLR4) were upregulated in both cells. Six and one genes were downregulated in Huh7 and HepG2, respectively, and no genes were downregulated in both cell lines. In summary, regorafenib and lenvatinib affect TLR signaling pathways in human hepatoma cell lines. Modulation of TLR signaling pathway may improve the treatment of HCC patients with refractory disease.
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spelling pubmed-72468702020-06-02 Different Mechanisms of Action of Regorafenib and Lenvatinib on Toll-Like Receptor-Signaling Pathways in Human Hepatoma Cell Lines Sasaki, Reina Kanda, Tatsuo Fujisawa, Mariko Matsumoto, Naoki Masuzaki, Ryota Ogawa, Masahiro Matsuoka, Shunichi Kuroda, Kazumichi Moriyama, Mitsuhiko Int J Mol Sci Article Multiple kinase inhibitors are available for patients with advanced hepatocellular carcinoma (HCC). It is largely unknown whether regorafenib or lenvatinib modulates innate immunity including Toll-like receptor (TLR)-signaling pathways in HCC. We performed real-time RT-PCR to investigate 84 TLR-associated gene expression levels and compared these gene expression levels in each hepatoma cells treated with or without regorafenib or lenvatinib. In response to regorafenib, nine and 10 genes were upregulated in Huh7 and HepG2 cells, respectively, and only C-X-C motif chemokine ligand 10 was upregulated in both cell lines. A total of 14 and 12 genes were downregulated in Huh7 and HepG2 cells, respectively, and two genes (Fos proto-oncogene, AP-1 transcription factor subunit, and ubiquitin conjugating enzyme E2 N) were downregulated in both cell lines. In response to lenvatinib, four and 16 genes were upregulated in Huh7 and HepG2 cells, respectively, and two genes (interleukin 1 alpha and TLR4) were upregulated in both cells. Six and one genes were downregulated in Huh7 and HepG2, respectively, and no genes were downregulated in both cell lines. In summary, regorafenib and lenvatinib affect TLR signaling pathways in human hepatoma cell lines. Modulation of TLR signaling pathway may improve the treatment of HCC patients with refractory disease. MDPI 2020-05-09 /pmc/articles/PMC7246870/ /pubmed/32397371 http://dx.doi.org/10.3390/ijms21093349 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sasaki, Reina
Kanda, Tatsuo
Fujisawa, Mariko
Matsumoto, Naoki
Masuzaki, Ryota
Ogawa, Masahiro
Matsuoka, Shunichi
Kuroda, Kazumichi
Moriyama, Mitsuhiko
Different Mechanisms of Action of Regorafenib and Lenvatinib on Toll-Like Receptor-Signaling Pathways in Human Hepatoma Cell Lines
title Different Mechanisms of Action of Regorafenib and Lenvatinib on Toll-Like Receptor-Signaling Pathways in Human Hepatoma Cell Lines
title_full Different Mechanisms of Action of Regorafenib and Lenvatinib on Toll-Like Receptor-Signaling Pathways in Human Hepatoma Cell Lines
title_fullStr Different Mechanisms of Action of Regorafenib and Lenvatinib on Toll-Like Receptor-Signaling Pathways in Human Hepatoma Cell Lines
title_full_unstemmed Different Mechanisms of Action of Regorafenib and Lenvatinib on Toll-Like Receptor-Signaling Pathways in Human Hepatoma Cell Lines
title_short Different Mechanisms of Action of Regorafenib and Lenvatinib on Toll-Like Receptor-Signaling Pathways in Human Hepatoma Cell Lines
title_sort different mechanisms of action of regorafenib and lenvatinib on toll-like receptor-signaling pathways in human hepatoma cell lines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246870/
https://www.ncbi.nlm.nih.gov/pubmed/32397371
http://dx.doi.org/10.3390/ijms21093349
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