Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1783538047623626752 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7246870 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT sasakireina differentmechanismsofactionofregorafenibandlenvatinibontolllikereceptorsignalingpathwaysinhumanhepatomacelllines AT kandatatsuo differentmechanismsofactionofregorafenibandlenvatinibontolllikereceptorsignalingpathwaysinhumanhepatomacelllines AT fujisawamariko differentmechanismsofactionofregorafenibandlenvatinibontolllikereceptorsignalingpathwaysinhumanhepatomacelllines AT matsumotonaoki differentmechanismsofactionofregorafenibandlenvatinibontolllikereceptorsignalingpathwaysinhumanhepatomacelllines AT masuzakiryota differentmechanismsofactionofregorafenibandlenvatinibontolllikereceptorsignalingpathwaysinhumanhepatomacelllines AT ogawamasahiro differentmechanismsofactionofregorafenibandlenvatinibontolllikereceptorsignalingpathwaysinhumanhepatomacelllines AT matsuokashunichi differentmechanismsofactionofregorafenibandlenvatinibontolllikereceptorsignalingpathwaysinhumanhepatomacelllines AT kurodakazumichi differentmechanismsofactionofregorafenibandlenvatinibontolllikereceptorsignalingpathwaysinhumanhepatomacelllines AT moriyamamitsuhiko differentmechanismsofactionofregorafenibandlenvatinibontolllikereceptorsignalingpathwaysinhumanhepatomacelllines |