ArticleStem cell research & therapy2023
Human menstrual blood-derived stem cells reverse sorafenib resistance in hepatocellular carcinoma cells through the hyperactivation of mitophagy.
Article in Stem cell research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- The molecular mechanisms of mitochondrial dynamics and mitophagy and their complex association with cancer drug resistance.Journal of translational medicine · 2025Pooled it
- Mitophagy interacts with mitochondrial dynamics and biogenesis, acting as a double-edged sword in digestive cancer.iScience · 2026Review
- Single-cell and spatial transcriptomics reveal Thbs1-CD36 crosstalk between Kupffer and hepatic stellate cells following mesenchymal stem cell-derived small extracellular vesicles transplantation, alleviating liver fibrosis.Journal of nanobiotechnology · 2026Article
- Advances in mitophagy research in hepatocellular carcinoma: mechanisms and therapeutic implications.Journal of gastrointestinal oncology · 2026Review
- Dual Roles of NIX/BNIP3L in Tumors: Friend or Foe.Biology · 2026Review
- Resistance of first-line targeted drugs in hepatocellular carcinoma: the epigenetic regulation mechanisms.Cell death & disease · 2025Review
- Bibliometric and visualized analysis of mitophagy in liver cancer from 1998 to 2024.Discover oncology · 2025Article
- Targeting Mitochondrial Quality Control for the Treatment of Triple-Negative Breast Cancer: From Molecular Mechanisms to Precision Therapy.Biomolecules · 2025Review
- Mitophagy in gastrointestinal tumors: mechanisms and new targets for immunotherapy.Frontiers in oncology · 2025Review
- Traditional Chinese Medicine Monomers and Their Derivatives as a Promising Therapeutic Tool for Hepatocellular Carcinoma by Activation of Mitophagy.Drug design, development and therapy · 2025Review
- Comprehensive review and updated analysis of DNA methylation in hepatocellular carcinoma: From basic research to clinical application.Clinical and translational medicine · 2024Review
- Article
- Human Menstrual Blood-Derived Stem Cells Protect against Tacrolimus-Induced Islet Dysfunction via Cystathionine β-Synthase Mediated IL-6/STAT3 Inactivation.Biomolecules · 2024Article
- Advances in hepatocellular carcinoma drug resistance models.Frontiers in medicine · 2024Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSorafenib is a first-line drug targeting the RTK-MAPK signalling pathway used to treat advanced hepatocellular carcinoma (HCC). However, tumour cells readily develop sorafenib resistance, limiting long-term therapy with this drug. In our previous study, we found that human menstrual blood-derived stem cells (MenSCs) altered the expression of some sorafenib resistance-associated genes in HCC cells. Therefore, we wanted to further explore the feasibility of MenSC-based combination therapy in treating sorafenib-resistant HCC (HCC-SR) cells.
methodsThe therapeutic efficiency of sorafenib was determined using CCK-8 (Cell Counting Kit-8), Annexin V/PI and clone formation assays in vitro and a xenograft mouse model in vivo. DNA methylation was determined using RT‒PCR and methylated DNA immunoprecipitation (MeDIP). Autophagy was detected by measuring LC3-II degradation and autophagosome maturation. Transmission electron microscopy identified autophagosomes and mitochondria. Physiological functions of mitochondria were assessed by measuring the ATP content, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (MMP).
resultsThe tumour suppressor genes BCL2 interacting protein 3 (BNIP3) and BCL2 interacting protein 3 like (BNIP3L) were silenced by promoter methylation and that BNIP3 and BNIP3L levels correlated negatively with sorafenib resistance in HCC-SR cells. Strikingly, MenSCs reversed sorafenib resistance. MenSCs upregulated BNIP3 and BNIP3L expression in HCC-SR cells via tet methylcytosine dioxygenase 2 (TET2)-mediated active demethylation. In HCC-SR cells receiving sorafenib and MenSC combination therapy, pressure from sorafenib and elevated BNIP3 and BNIP3L levels disrupted balanced autophagy. Hyperactivation of mitophagy significantly caused severe mitochondrial dysfunction and eventually led to the autophagic death of HCC-SR cells.
conclusionsOur research suggests that combining sorafenib and MenSCs may be a potentially new strategy to reverse sorafenib resistance in HCC-SR cells.
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