Emodin suppresses angiogenesis and metastasis in anaplastic thyroid cancer by affecting TRAF6‑mediated pathways in vivo and in vitro

Shi,Guo‑Hua; Zhou,Lin

doi:10.3892/mmr.2018.9510

Emodin suppresses angiogenesis and metastasis in anaplastic thyroid cancer by affecting TRAF6‑mediated pathways in vivo and in vitro

Authors:
- Guo‑Hua Shi
- Lin Zhou
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Affiliations: Department of Nuclear Medicine, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China, Department of Minimally Invasive Surgery, Zhejiang Chinese Medicine and Western Medicine Integrated Hospital, Hangzhou, Zhejiang 310016, P.R. China
Published online on: September 26, 2018 https://doi.org/10.3892/mmr.2018.9510
Pages: 5191-5197

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Abstract

Emodin has been recognized to be an anti‑cancer agent against a number of types of human cancer. It was demonstrated that TNF receptor‑associated factor 6 (TRAF6) was correlated with cancer angiogenesis and metastasis. The present study confirmed the association between TRAF6 and the angiogenesis/metastasis of anaplastic thyroid cancer (ATC). The anti‑angiogenesis and metastatic effects of emodin, in addition to its molecular mechanisms in ATC, were investigated. A total of two ATC cell lines, namely 8505c and SW1736, were studied. ATC cells were implanted into nude mice to form xenografts or to establish lung metastasis models. Emodin was used to incubate ATC cells or to treat animals orally. An MTT assay was used to assess cell proliferation. A wound healing assay was employed to evaluate cell migration. ELISA analysis was used to detect the vascular endothelial growth factor (VEGF) content. Western blotting was used to determine the protein expression levels. In the in vivo study, cancer angiogenesis was assessed by micro vascular density measurement. The lung metastatic rate was the criterion for cancer metastasis. The results of the present study demonstrated that the proliferation of ATC was inhibited by emodin. The activation of the TRAF6/hypoxia inducible factor (HIF)‑1α/VEGF and TRAF6/basigin (CD147)/matrix metalloproteinase‑9 (MMP9) pathways were associated with the angiogenesis and metastasis of ATC. In a concentration‑dependent manner, emodin inhibited the TRAF6/HIF‑1α/VEGF and TRAF6/CD147/MMP9 signaling pathways to suppress angiogenesis and metastasis. In conclusion, emodin exerted anti‑angiogenic and anti‑metastatic activities in ATC by affecting TRAF6‑mediated pathways.

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