The retinoblastoma (Rb) protein regulates ferroptosis induced by sorafenib in human hepatocellular carcinoma cells
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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Rb suppresses ferroptosis in response to sorafenib, suggesting Rb status may help select ferroptosis-sensitive tumors for sorafenib.
“Recently, the retinoblastoma protein (Rb) was found to suppress ferroptosis in response to sorafenib [30], suggesting that Rb status may aid in selecting ferroptosis-sensitive tumors, at least for sorafenib.”
From Ferroptosis: Death by Lipid Peroxidation (2016) · cites this paper as [30]
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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
- Venue
- Cancer Letters
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 356
- Issue
- 2
- Pages
- 971-977
- ISSN
- 0304-3835 (ISSN-L)
- 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
- Locations
- Cancer Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ligue Contre le Cancer
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › 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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