Cited by 374Ferroptosis and cancer prognosisHepatocellular Carcinoma Treatment and PrognosisCancer-related Molecular Pathways

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The retinoblastoma (Rb) protein regulates ferroptosis induced by sorafenib in human hepatocellular carcinoma cells

Louandre, Christophe, Marcq, Ingrid, Bouhlal, Hicham, Lachaier, Emma, Godin, Corinne, Saidak, Zuzana, François, Catherine, Chatelain, Denis, Debuysscher, Véronique, Barbare, Jean-Claude, Chauffert, Bruno, Galmiche, Antoine·2015·Cancer Letters

DOI 10.1016/j.canlet.2014.11.014

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Abstract

Sorafenib is the treatment of reference for advanced hepatocellular carcinoma (HCC), the most frequent form of primary liver tumour. The loss of function of the retinoblastoma (Rb) protein is an important event during liver carcinogenesis, but it is unclear whether the Rb status modulates the response of HCC cells to sorafenib. Here, we examined this question in HCC cells with reduced levels of Rb achieved through stable RNA interference. We show that HCC cells with reduced levels of Rb exhibit a two- to threefold increase in cell death induction upon exposure to sorafenib compared with controls. Sorafenib treatment of Balb/c nude mice that received tumour xenografts derived from HCC cells with reduced Rb levels resulted in complete tumour regression in 50% of the animals treated, compared with tumour stabilization in mice that received control cells. We show that, upon exposure to sorafenib, the Rb-negative status of HCC cells promotes the occurrence of ferroptosis, a form of oxidative necrosis. The findings highlight the role of Rb in the response of HCC cells to sorafenib and the regulation of ferroptosis.

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Authors: Louandre, C., Marcq, I., Bouhlal, H., Lachaier, E., Godin, C., Saidak, Z., François, C., Chatelain, D., Debuysscher, V., Barbare, J.-C., Chauffert, B., & Galmiche, A.
Affiliations: Centre Hospitalier Universitaire Amiens-Picardie (FR)
Université de Picardie Jules Verne (FR)
Corresponding author: Galmiche, Antoine
ORCID: Louandre, Christophe
Marcq, Ingrid
Bouhlal, Hicham
Godin, Corinne
Saidak, Zuzana
François, Catherine
Chatelain, Denis
Barbare, Jean-Claude
Galmiche, Antoine
Venue: Cancer Letters
Publisher: Elsevier BV
Published: 2015-01
Volume: 356
Issue: 2
Pages: 971-977
ISSN: 0304-3835 (ISSN-L)
DOI: 10.1016/j.canlet.2014.11.014
OpenAlex: W1966824235
Cited by: 374
References: 29
Citations by year: 2026: 12 · 2025: 24 · 2024: 41 · 2023: 50 · 2022: 76 · 2021: 71 · 2020: 39 · 2019: 21 · 2018: 16 · 2017: 12 · 2016: 7 · 2015: 4
FWCI: 6.14
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Cancer Letters (publishedVersion)
PubMed (publishedVersion)
Funders: Ligue Contre le Cancer
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords: retinoblastoma protein, ferroptosis, sorafenib, hepatocellular carcinoma, drug response, tumor regression, RNA interference, tumor xenografts
MeSH terms: Sorafenib, Animals, Antineoplastic Agents, Female, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Mice, Inbred BALB C, Mice, Nude, Mitochondria, Necrosis, Niacinamide, Phenylurea Compounds, Tumor Cells, Cultured, Blotting, Western, Retinoblastoma Protein, Apoptosis, Reactive Oxygen Species, Oxidative Stress, Xenograft Model Antitumor Assays, Cell Proliferation, Mice

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The retinoblastoma (Rb) protein regulates ferroptosis induced by sorafenib in human hepatocellular carcinoma cells

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