Journal of Cancer Research and Clinical Oncology

, Volume 144, Issue 12, pp 2329–2337 | Cite as

Role of ferroptosis in hepatocellular carcinoma

  • Jianhua Nie
  • Binlin Lin
  • Meng Zhou
  • Li Wu
  • Tongsen ZhengEmail author
Review – Cancer Research



Hepatocellular carcinoma (HCC) is a complicated disease with low survival rate due to frequent recurrence and the lack of efficient therapies. For advanced HCC, sorafenib, as the only approved first-line drug for HCC, improves the survival to some extent, but depressingly with severe adverse effects and emerging resistance conditions, which cause a poor prognosis. Ferroptosis is a new recognized way of non-apoptosis-regulated cell death, characterized by the iron-dependent accumulation of lipid hydroperoxides, showing a tremendous promising in the therapy of cancer, especially in HCC. To provide ideas for the diagnosis and treatment of HCC, we summarized the role of ferroptosis in HCC.


The relevant literature from PubMed is reviewed in this article.


Interestingly enough, investigators have found sorafenib can induce ferroptosis in HCC. Moreover, recent researches reported increasing pathways and mechanisms related to ferroptosis in HCC such as TP53 and Rb, and strategies to improve sorafenib resistance by targeting ferroptosis. In addition, other drugs were reported to induce ferroptosis in HCC such as erastin and showed good efficacy in vivo and in vitro.


In this review, we summarize pathways and mechanisms of ferroptosis in HCC and other digestive system neoplasms such as gastric cancer, pancreatic cancer and colorectal cancer and point out the trends of ferroptosis in HCC.


Hepatocellular carcinoma Ferroptosis Sorafenib Lipid metabolism Iron Therapy 



Hepatocellular carcinoma


Regulated cell death


Nuclear factor erythroid 2-related factor 2


Ribosomal protein L8


Iron-responsive element-binding protein 2


ATP synthase F0 complex subunit C3


Citrate synthase


Tetratricopeptide repeat domain 35


Acyl-CoA synthetase family member 2




Reactive oxygen species


Glutathione peroxidase 4


Diffuse large B-cell lymphoma


Renal cell carcinoma


Pancreatic cancer








Kelch-like ECH-associated protein 1


V-maf avian musculoaponeurotic fibrosarcoma oncogene homolog


Quinone oxidoreductase 1


Heme oxygenase-1


Ferritin heavy chain 1




Hypoxia-inducible factor 1-alpha


Sigma 1 receptor


CDGSH iron sulfur domain 1


Ser 47


Acyl-CoA synthetase long-chain family member 4


5-Hydroxyeicosatetraenoic acid


Low-density lipoprotein docosahexaenoic acid


Gastric cancer


Colorectal cancer


Cysteine dioxygenase 1


Pancreatic ductal adenocarcinoma


Cotylenin A


Phenethyl isothiocyanate




Heatshock 70-kDa protein 5




Arachidonate lipoxygenase


Nuclear receptor coactivator 4


C/EBP-homologous protein


Tumor necrosis factor-related apoptosis-inducing ligand





We are grateful to the staff at the GI oncology of cancer hospital of HMU. And we thank Kainan Kang for his critical reading of the manuscript.


This study was funded by the National Natural Scientific Foundation of China (No. 81302060, No.81472322 and No. 81672930), the national youth talent support program for TS Zheng, the Natural Science Foundation of Heilongjiang Province (LC201437/H1617), China Postdoctoral Science Foundation (No. 2015T80369 and No. 2014M560271), and Heilongjiang Postdoctoral Science Foundation (No. LBH-Z14142 and No. LBH-TZ1615), the Fok Ying Tung Education Foundation (No. 151037), the Academician Yu Weihan Outstanding youth foundation of Harbin Medical University for TS Zheng. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Compliance with ethical standards

Conflict of interest

Authors declare no conflict of interests.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Gastrointestinal Medical OncologyCancer Hospital of Harbin Medical UniversityHarbinPeople’s Republic of China
  2. 2.Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education)Harbin Medical UniversityHarbinPeople’s Republic of China

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