TLR7 agonist induced repression of hepatocellular carcinoma via the TLR7-IKK-NF-κB-IL6 signaling pathway
Toll-like receptors (TLRs) are key members of innate immunity, involved in the defense against diseases, and evidence has revealed that TLR4/5 is involved in the carcinogenesis of hepatic cancer. TLR7 belongs to the TLR family, and its roles in immune-associated hepatic diseases have been well chara...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4840696/ https://www.ncbi.nlm.nih.gov/pubmed/27123047 http://dx.doi.org/10.3892/ol.2016.4329 |
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author | REN, XINGBIN WANG, FEI JI, BAOJU GAO, CHUNHAI |
author_facet | REN, XINGBIN WANG, FEI JI, BAOJU GAO, CHUNHAI |
author_sort | REN, XINGBIN |
collection | PubMed |
description | Toll-like receptors (TLRs) are key members of innate immunity, involved in the defense against diseases, and evidence has revealed that TLR4/5 is involved in the carcinogenesis of hepatic cancer. TLR7 belongs to the TLR family, and its roles in immune-associated hepatic diseases have been well characterized; however, the consequences of agonist targeting of TLR7 in hepatic cancer have not previously been reported. The present study aimed to investigate the effects and underlying mechanisms of Imiquimod, a TLR7 agonist, on hepatic carcinogenesis by affecting the self-renewal of hepatic cancer stem cells. To detect the effects of this TLR7 agonist on hepatic cancer cells an MTT assay, mammosphere formation assay, ALDEFLUOR™ fluorescence-based stem cell sorting was used, and the potential signaling involved in the mechanism was investigated by western blot analysis. The TLR7 agonist Imiquimod demonstrated inhibitory effects on the cell proliferation and mammosphere formation of hepatic cells and stem cells, and decreased stem cell number (P<0.01). These effects may be achieved via the TLR7/IκB kinase/nuclear factor-κB/interleukin-6 signaling pathway, with decreased levels of Snail expression. The present study demonstrated the effects and mechanisms of the TLR7 agonist on hepatic cancer occurred via suppression of the self-renewal of cancer stem cells, indicating novel potential functions of the TLR7 agonist in the treatment of HCC. |
format | Online Article Text |
id | pubmed-4840696 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-48406962016-04-27 TLR7 agonist induced repression of hepatocellular carcinoma via the TLR7-IKK-NF-κB-IL6 signaling pathway REN, XINGBIN WANG, FEI JI, BAOJU GAO, CHUNHAI Oncol Lett Articles Toll-like receptors (TLRs) are key members of innate immunity, involved in the defense against diseases, and evidence has revealed that TLR4/5 is involved in the carcinogenesis of hepatic cancer. TLR7 belongs to the TLR family, and its roles in immune-associated hepatic diseases have been well characterized; however, the consequences of agonist targeting of TLR7 in hepatic cancer have not previously been reported. The present study aimed to investigate the effects and underlying mechanisms of Imiquimod, a TLR7 agonist, on hepatic carcinogenesis by affecting the self-renewal of hepatic cancer stem cells. To detect the effects of this TLR7 agonist on hepatic cancer cells an MTT assay, mammosphere formation assay, ALDEFLUOR™ fluorescence-based stem cell sorting was used, and the potential signaling involved in the mechanism was investigated by western blot analysis. The TLR7 agonist Imiquimod demonstrated inhibitory effects on the cell proliferation and mammosphere formation of hepatic cells and stem cells, and decreased stem cell number (P<0.01). These effects may be achieved via the TLR7/IκB kinase/nuclear factor-κB/interleukin-6 signaling pathway, with decreased levels of Snail expression. The present study demonstrated the effects and mechanisms of the TLR7 agonist on hepatic cancer occurred via suppression of the self-renewal of cancer stem cells, indicating novel potential functions of the TLR7 agonist in the treatment of HCC. D.A. Spandidos 2016-05 2016-03-16 /pmc/articles/PMC4840696/ /pubmed/27123047 http://dx.doi.org/10.3892/ol.2016.4329 Text en Copyright: © Ren et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles REN, XINGBIN WANG, FEI JI, BAOJU GAO, CHUNHAI TLR7 agonist induced repression of hepatocellular carcinoma via the TLR7-IKK-NF-κB-IL6 signaling pathway |
title | TLR7 agonist induced repression of hepatocellular carcinoma via the TLR7-IKK-NF-κB-IL6 signaling pathway |
title_full | TLR7 agonist induced repression of hepatocellular carcinoma via the TLR7-IKK-NF-κB-IL6 signaling pathway |
title_fullStr | TLR7 agonist induced repression of hepatocellular carcinoma via the TLR7-IKK-NF-κB-IL6 signaling pathway |
title_full_unstemmed | TLR7 agonist induced repression of hepatocellular carcinoma via the TLR7-IKK-NF-κB-IL6 signaling pathway |
title_short | TLR7 agonist induced repression of hepatocellular carcinoma via the TLR7-IKK-NF-κB-IL6 signaling pathway |
title_sort | tlr7 agonist induced repression of hepatocellular carcinoma via the tlr7-ikk-nf-κb-il6 signaling pathway |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4840696/ https://www.ncbi.nlm.nih.gov/pubmed/27123047 http://dx.doi.org/10.3892/ol.2016.4329 |
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