Abstract
Purpose
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.
Methods
The relevant literature from PubMed is reviewed in this article.
Results
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.
Conclusion
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.
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Abbreviations
- HCC:
-
Hepatocellular carcinoma
- RCD:
-
Regulated cell death
- NRF2:
-
Nuclear factor erythroid 2-related factor 2
- RPL8:
-
Ribosomal protein L8
- IREB2:
-
Iron-responsive element-binding protein 2
- ATP5G3:
-
ATP synthase F0 complex subunit C3
- CS:
-
Citrate synthase
- TTC35:
-
Tetratricopeptide repeat domain 35
- ACSF2:
-
Acyl-CoA synthetase family member 2
- GSH:
-
Glutathione
- ROS:
-
Reactive oxygen species
- GPX4:
-
Glutathione peroxidase 4
- DLBCL:
-
Diffuse large B-cell lymphoma
- RCC:
-
Renal cell carcinoma
- PC:
-
Pancreatic cancer
- SSZ:
-
Sulfasalazine
- DFX:
-
Deferoxamine
- Rb:
-
Retinoblastoma
- Keap1:
-
Kelch-like ECH-associated protein 1
- Maf:
-
V-maf avian musculoaponeurotic fibrosarcoma oncogene homolog
- NQO1:
-
Quinone oxidoreductase 1
- HO1:
-
Heme oxygenase-1
- FTH1:
-
Ferritin heavy chain 1
- MT:
-
Metallothionein
- HIF1α:
-
Hypoxia-inducible factor 1-alpha
- S1R:
-
Sigma 1 receptor
- CISD1:
-
CDGSH iron sulfur domain 1
- S47:
-
Ser 47
- ACSL4:
-
Acyl-CoA synthetase long-chain family member 4
- 5-HETE:
-
5-Hydroxyeicosatetraenoic acid
- LDL–DHA:
-
Low-density lipoprotein docosahexaenoic acid
- GC:
-
Gastric cancer
- CRC:
-
Colorectal cancer
- CDO1:
-
Cysteine dioxygenase 1
- PDAC:
-
Pancreatic ductal adenocarcinoma
- CN-A:
-
Cotylenin A
- PEITC:
-
Phenethyl isothiocyanate
- PL:
-
Piperlongumine
- HSPA5:
-
Heatshock 70-kDa protein 5
- LOX:
-
Lipoxygenases
- ALOX:
-
Arachidonate lipoxygenase
- NCOA4:
-
Nuclear receptor coactivator 4
- CHOP:
-
C/EBP-homologous protein
- TRAIL:
-
Tumor necrosis factor-related apoptosis-inducing ligand
- DPP4:
-
Dipeptidyl-peptidase-4
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Acknowledgements
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.
Funding
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.
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Nie, J., Lin, B., Zhou, M. et al. Role of ferroptosis in hepatocellular carcinoma. J Cancer Res Clin Oncol 144, 2329–2337 (2018). https://doi.org/10.1007/s00432-018-2740-3
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DOI: https://doi.org/10.1007/s00432-018-2740-3