TLR7 agonist induced repression of hepatocellular carcinoma via the TLR7-IKK-NF-κB-IL6 signaling pathway

Ren,Xingbin; Wang,Fei; Ji,Baoju; Gao,Chunhai

doi:10.3892/ol.2016.4329

TLR7 agonist induced repression of hepatocellular carcinoma via the TLR7-IKK-NF-κB-IL6 signaling pathway

Authors:
- Xingbin Ren
- Fei Wang
- Baoju Ji
- Chunhai Gao
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Affiliations: Department of Clinical Laboratory, Linyi People's Hospital, Linyi, Shandong 276003, P.R China, Department of Pain Management, Linyi People's Hospital, Linyi, Shandong 276003, P.R China
Published online on: March 16, 2016 https://doi.org/10.3892/ol.2016.4329
Pages: 2965-2970
Copyright: © Ren et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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