ArticleBMC cancer2020
Modulation of SIRT3 expression through CDK4/6 enhances the anti-cancer effect of sorafenib in hepatocellular carcinoma cells.
Article in BMC cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Chromatin chronicles: Unlocking the therapeutic potential of histone modifiers in hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2026Review
- Mechanisms of lactylation modification in hepatocellular carcinoma treatment resistance.Gastroenterology report · 2026Review
- Emerging Role of Sirtuins-Mediated Ferroptosis in Hepatocellular Carcinoma Progression: Mechanisms and Therapeutic Perspectives.Journal of hepatocellular carcinoma · 2026Review
- CDK4/6-targeted therapy for gastrointestinal cancers: from resistance mechanisms to immuno-combination strategies guided by biomarkers.Frontiers in immunology · 2026Review
- Sirtuins as Therapeutic Targets for Treating Cancer, Metabolic Diseases, and Neurodegenerative Diseases.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Is SIRT3 and Mitochondria a Reliable Target for Parkinson's Disease and Aging? A Narrative Review.Molecular neurobiology · 2025Review
- Classification of the LC4 Primarily-like Cell Line-Recapitulating a CDK4 Overexpressing Immune Evasive HIV-HCV-Induced HCC.Viruses · 2025Article
- SIRT3, a New Hope in Liver Diseases from Pathogenic Mechanisms to Therapeutic Strategies.Current pharmaceutical biotechnology · 2025Review
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- Succinate-Directed Approaches for Warburg Effect-Targeted Cancer Management, an Alternative to Current Treatments?Cancers · 2023Review
- LncRNA SATB2-AS1 overexpression represses the development of hepatocellular carcinoma through regulating the miR-3678-3p/GRIM-19 axis.Cancer cell international · 2023Article
- Mitochondrial Dysfunction: A Cellular and Molecular Hub in Pathology of Metabolic Diseases and Infection.Journal of clinical medicine · 2023Review
- The sirtuin family in health and disease.Signal transduction and targeted therapy · 2022Review
- Cancer-derived extracellular succinate: a driver of cancer metastasis.Journal of biomedical science · 2022Review
- Review
- SIRT3 and Metabolic Reprogramming Mediate the Antiproliferative Effects of Whey in Human Colon Cancer Cells.Cancers · 2021Article
- Elevated miR-16-5p induces somatostatin receptor 2 expression in neuroendocrine tumor cells.PloS one · 2020Article
- Mitochondrial Sirtuin 3: New emerging biological function and therapeutic target.Theranostics · 2020Review
- Cyclin-Dependent Kinase 4/6 Inhibitors: A Potential Breakthrough Therapy for Malignancies of Gastrointestinal Tract.In vivo (Athens, Greece)Review
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundHepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths worldwide. The only drug currently approved for clinical use in the treatment of advanced HCC is sorafenib. However, many patients with HCC show reduced sensitivity to sorafenib during treatment. SIRT3, a member of the mammalian sirtuin family, is a tumor suppressor in certain tumor types. However, only few studies have investigated the effects of SIRT3 on tumor prognosis and sorafenib sensitivity in patients with HCC. Here, we aimed to investigate the correlation between SIRT3 expression and glucose metabolism and proliferation in HCC and discover effective compounds that increase endogenous SIRT3 modulation effect of sorafenib.
methodsTo determine the correlation between SIRT3 and glucose related proteins, immunostaining was performed with liver cancer tissue using various antibodies. To investigate whether the expression of SIRT3 in HCC is related to the resistance to sorafenib, we treated sorafenib after the modulation of SIRT3 levels in HCC cell lines (overexpression in Huh7, knockdown in HepG2). We also employed PD0332991 to modulate the SIRT3 expression in HCC cell and conducted functional assays.
resultsSIRT3 expression was downregulated in high glycolytic and proliferative HCC cells of human patients, xenograft model and HCC cell lines. Moreover, SIRT3 expression was downregulated after sorafenib treatment, resulting in reduced drug sensitivity in HCC cell lines. To enhance the anti-tumor effect of sorafenib, we employed PD0332991 (CDK4/6-Rb inhibitor) based on the correlation between SIRT3 and phosphorylated retinoblastoma protein in HCC. Notably, combined treatment with sorafenib and PD0332991 showed an enhancement of the anti-tumor effect in HCC cells.
conclusionsOur data suggest that the modulation of SIRT3 by CDK4/6 inhibition might be useful for HCC therapy together with sorafenib, which, unfortunately, has limited efficacy and whose use is often associated with drug resistance.
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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 Socratic graph.