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...

Descripción completa

Detalles Bibliográficos
Autores principales: REN, XINGBIN, WANG, FEI, JI, BAOJU, GAO, CHUNHAI
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2016
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
_version_ 1782428301680181248
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
work_keys_str_mv AT renxingbin tlr7agonistinducedrepressionofhepatocellularcarcinomaviathetlr7ikknfkbil6signalingpathway
AT wangfei tlr7agonistinducedrepressionofhepatocellularcarcinomaviathetlr7ikknfkbil6signalingpathway
AT jibaoju tlr7agonistinducedrepressionofhepatocellularcarcinomaviathetlr7ikknfkbil6signalingpathway
AT gaochunhai tlr7agonistinducedrepressionofhepatocellularcarcinomaviathetlr7ikknfkbil6signalingpathway