Emodin treatment of papillary thyroid cancer cell lines <em>in</em> <em>vitro</em> inhibits proliferation and enhances apoptosis via downregulation of NF‑κB and its upstream TLR4 signaling

Liu,Xin; Wei,Wei; Wu,Yue-Zhang; Wang,Yuan; Zhang,Wei-Wei; Wang,Yong-Ping; Dong,Xiao-Ping; Shi,Qi

doi:10.3892/ol.2023.14101

Emodin treatment of papillary thyroid cancer cell lines in vitro inhibits proliferation and enhances apoptosis via downregulation of NF‑κB and its upstream TLR4 signaling

Authors:
- Xin Liu
- Wei Wei
- Yue-Zhang Wu
- Yuan Wang
- Wei-Wei Zhang
- Yong-Ping Wang
- Xiao-Ping Dong
- Qi Shi
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Affiliations: Basic Medical College, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550025, P.R. China, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Head and Neck Surgery, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China, National Key‑Laboratory of Intelligent Tracing and Forecasting for Infectious Disease, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, P.R. China
Published online on: October 13, 2023 https://doi.org/10.3892/ol.2023.14101
Article Number: 514
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Thyroid cancer is one of the most common types of endocrine malignancy. In addition to surgical treatment, it is very important to find new treatment methods. The aim of the present study was to evaluate the effect of 1,3,8‑trihydroxy‑6‑methylanthraquinone (emodin) on cellular NF‑κB components and the upstream regulatory pathway of toll‑like receptor 4 (TLR4) signaling, as well as the invasion and migration of papillary thyroid carcinoma (PTC) cells. The protein expression of NF‑κB components p65 and p50 and their phosphorylated (p‑) forms in the sections of PTC tissues was measured by individual immunohistochemical assays. PTC cell lines TPC‑1 and IHH4 were exposed to 20 and 40 µM emodin for 24 h. The levels of the NF‑κB components p65, p50, c‑Rel, p‑p65 and p‑p50, elements in TLR4 signaling, including TLR4, MYD88 innate immune signal transduction adaptor (MyD88), interferon regulatory factor 3, AKT and MEK, and proliferative and apoptotic biomarkers, including c‑Myc, cyclin D1, proliferating cell nuclear antigen, Bcl‑2 and Bax, were evaluated by western blotting and immunofluorescent assays. The invasion and migration of PTC cell lines exposed to emodin were tested by plate colony and wound healing assay. Compared with hyperplasia tissue, the expression levels of NF‑κB components p65 and p50, and p‑p65 and p‑p50 in PTC tissue were significantly increased. Treatment of PTC cell lines with emodin lead to significantly reduced levels of the aforementioned NF‑κB components, accompanied by markedly downregulated TLR4 signaling. MYD 88‑dependent and ‑independent pathways, are also significantly down‑regulated. Downregulation of proliferative factors and activation of apoptotic factors were observed in the cell lines following treatment with emodin. Consequently, inhibition of the invasion and migration activities were observed in the emodin‑treated PTC cells. Emodin could inhibit proliferation and promote apoptosis of PTC cells, which is dependent on the downregulation of cellular NF‑κB and the TLR4 signaling pathway.

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