ArticleAging2019
Mitochondrial metabolic study guided by proteomics analysis in hepatocellular carcinoma cells surviving long-term incubation with the highest dose of sorafenib.
Article in Aging, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Article
- Mitochondrial-Based Nanomedicine in Treatment of Liver Cancer.Molecular biotechnology · 2026Review
- Metabolic reprogramming-driven resistance to multi-kinase inhibitors in hepatocellular carcinoma: molecular mechanisms and therapeutic opportunities.Molecular cancer · 2026Review
- Article
- Emerging Roles of NDUFS8 Located in Mitochondrial Complex I in Different Diseases.Molecules (Basel, Switzerland) · 2022Review
- Sorafenib and nitazoxanide disrupt mitochondrial function and inhibit regrowth capacity in three-dimensional models of hepatocellular and colorectal carcinoma.Scientific reports · 2022Article
- Identifying Potential Mitochondrial Proteome Signatures Associated with the Pathogenesis of Pulmonary Arterial Hypertension in the Rat Model.Oxidative medicine and cellular longevity · 2022Article
- Glucometabolic reprogramming: From trigger to therapeutic target in hepatocellular carcinoma.Frontiers in oncology · 2022Review
- Cell-cycle and apoptosis related and proteomics-based signaling pathways of human hepatoma Huh-7 cells treated by three currently used multi-RTK inhibitors.Frontiers in pharmacology · 2022Article
- Lipophilic Cations Rescue the Growth of Yeast under the Conditions of Glycolysis Overflow.Biomolecules · 2020Article
- Identification ofWorld journal of clinical cases · 2020Article
- Emerging roles and the regulation of aerobic glycolysis in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sorafenib is the standard first-line systemic therapy for hepatocellular carcinoma (HCC). However, the low objective response rates in clinical studies suggest the existence of certain HCC cells that are inherently insensitive to sorafenib. To understand the molecular basis of insensitivity of HCC cells to sorafenib, this study developed 3 kinds of insensitive HCC cells through exposure to various concentrations of sorafenib and performed a quantitative proteome analysis of the surviving HepG2 cells. 520 unique proteins were concentration-dependently upregulated by sorafenib. Bioinformatics-assisted analysis of 520 proteins revealed that the metabolic pathways involved in central carbon metabolism were significantly enriched, and 102 mitochondrial proteins, especially components of the electron transport chain (ETC), were incrementally upregulated in the 3 kinds of insensitive cells. Conversely, we identified a rapid holistic inhibitory effect of sorafenib on mitochondrial function by the direct targeting of the complex I-linked electron transport and the uncoupling of mitochondrial oxidative phosphorylation (OXHPOS) in HCC cells. Core metabolic reprogramming involved in a compensatory upregulation of OXHPOS combined with elevated glycolysis supports the survival of HCC cells under the highest dose of sorafenib treatment. Altogether, our work thus elaborates an ETC inhibitor and unveils the proteomic landscape of metabolic reprogramming in drug insensitivity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.