Pristimerin effectively inhibits the malignant phenotypes of uveal melanoma cells by targeting NF‑κB pathway

Zhang,Biao; Zhang,Jing; Pan,Jingxuan

doi:10.3892/ijo.2017.4079

Pristimerin effectively inhibits the malignant phenotypes of uveal melanoma cells by targeting NF‑κB pathway

Authors:
- Biao Zhang
- Jing Zhang
- Jingxuan Pan
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Affiliations: Institute of Tumor Pharmacology, College of Pharmacy, Jinan University, Guangzhou, Guangdong 510060, P.R. China
Published online on: July 25, 2017 https://doi.org/10.3892/ijo.2017.4079
Pages: 887-898

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Abstract

Uveal melanoma (UM) is a highly aggressive intraocular malignancy that lacks any effective targeted-therapy. Neither survival nor prognosis has been improved for the past decades in patients with metastatic UM. NF‑κB pathway is reported to be abnormally activated in UM. However, the role of NF‑κB pathway as a potential therapeutical target in UM remains unclear. Here, the effect of pristimerin, a potent inhibitor of NF‑κB pathway, on UM cells in terms of growth, apoptosis, motility, invasion and cancer stem-like cells (CSCs) was evaluated in vitro. We showed that pristimerin suppressed tumor necrosis factor α (TNFα)-induced IκBα phosphorylation, translocation of p65, and expression of NF‑κB-dependent genes. Moreover, pristimerin decreased cell viability and clonogenic ability of UM cells. A synergistic effect was observed in the treatment of pristimerin combined with vinblastine, a frontline therapeutic agent, in UM. Pristimerin led to a significant increase in the Annexin V+ cell population as measured by flow cytometry. We also observed that pristimerin impaired the abilities of migration and invasion in UM cells. Furthermore, pristimerin eliminated the ALDH+ cells and weakened serial re-plating ability of melanosphere. Collectively, pristimerin shows remarkable anticancer activities in UM cells through inactivating NF‑κB pathway, revealing that pristimerin may be a promising therapeutic agent in UM.

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