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Research Paper|Volume 16, Issue 2|pp 1767—1780

Tremella fuciformis polysaccharides induce ferroptosis in Epstein–Barr virus-associated gastric cancer by inactivating NRF2/HO-1 signaling

Wencheng Kong1,2, Xinchun Liu1, Hangzhang Zhu1, Sixing Zheng1, Guang Yin1, Panpan Yu1, Yuqiang Shan1, Shenglin Ma3, Rongchao Ying1, Huicheng Jin1
  • 1Department of Gastroenterological Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, P.R. China
  • 2Zhejiang Province Key Laboratory of Anticancer Drug Research, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang Province, P.R. China
  • 3Translational Medicine Research Center, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, P.R. China
Received: July 13, 2023Accepted: October 24, 2023Published: January 19, 2024
https://doi.org/10.18632/aging.205457

Copyright: © 2024 Kong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Approximately 10% of gastric cancers are associated with Epstein–Barr virus (EBV). Tremella fuciformis polysaccharides (TFPs) are characterized by antioxidative and anti-inflammatory effects in different diseases. However, whether TFP improves EBV-associated gastric cancer (EBVaGC) has never been explored. The effects of TFP on EBV-infected GC cell viability were determined using a CCK-8 assay and flow cytometry. Western blotting and RT–qPCR were performed to explore the expression of ferroptosis-related proteins. The CCK-8 assay showed that TFP decreased EBV-infected GC cell viability in a dose- and time-dependent manner. Flow cytometry assays indicated that TFP significantly induced EBV-infected GC cell death. TFP also reduced the migratory capacity of EBV-infected GC cells. Furthermore, treatment with TFP significantly increased the mRNA levels of PTGS2 and Chac1 in EBV-infected GC cells. Western blot assays indicated that TFP suppressed the expression of NRF2, HO-1, GPX4 and xCT in EBV-infected GC cells. More importantly, overexpression of NRF2 could obviously rescue TFP-induced downregulation of GPX4 and xCT in EBV-infected GC cells. In summary, we showed novel data that TFP induced ferroptosis in EBV-infected GC cells by inhibiting NRF2/HO-1 signaling. The current findings may shed light on the potential clinical application of TFP in the treatment of EBVaGC.