Affinage

FDXR

NADPH:adrenodoxin oxidoreductase, mitochondrial · UniProt P22570

Length
491 aa
Mass
53.8 kDa
Annotated
2026-06-09
100 papers in source corpus 9 papers cited in narrative 9 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/5 claims corpus-supported (80%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FDXR encodes the mitochondrial ferredoxin reductase that transfers electrons from NADPH to ferredoxins (including FDX2), the essential entry point for iron-sulfur cluster biosynthesis and heme formation, as established by biallelic loss-of-function mutations that cause auditory/peripheral neuropathy and optic atrophy in humans and that fail to complement deletion of the yeast ortholog ARH1 (PMID:28965846, PMID:30250212). Loss of FDXR function deregulates mitochondrial iron homeostasis, producing mitochondrial iron overload, membrane depolarization, respiratory chain dysfunction, and downstream neurodegeneration, gliosis, and neuroinflammation (PMID:32499495, PMID:30250212); AAV-mediated restoration of FDXR is sufficient to recover respiratory chain complex activity and reverse the neuropathy and optic phenotypes, confirming these defects are direct consequences of FDXR deficiency (PMID:32995353). Beyond its enzymatic role, FDXR participates in a tumor-suppressor circuit in which its loss elevates IRP2 via FDX2, leading IRP2 to bind an iron response element in the TP73 3'UTR and destabilize p73, a relationship reinforced by in vivo genetic epistasis between Fdxr and Trp73 (PMID:32304229). FDXR additionally sustains fatty acid oxidation in ER+ breast cancer cells by maintaining CPT1A expression (PMID:37207154), and physically associates with the tumor suppressor FHIT in mitochondria to modulate ROS production and apoptosis under oxidative stress (PMID:30770797). As a p53-regulated gene, FDXR transcription is robustly and dose-dependently induced by ionizing radiation across multiple splice variants, making it a biomarker of radiation exposure (PMID:33113898, PMID:29330481).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2017 High

    Establishing that FDXR is essential in humans answered whether the mitochondrial ferredoxin reductase has a non-redundant physiological role, linking its loss to a defined neurodegenerative disease via iron-sulfur cluster and heme biosynthesis.

    Evidence Whole-exome sequencing of affected families, patient fibroblast iron homeostasis assays, and yeast ARH1-deletion complementation

    PMID:28965846

    Open questions at the time
    • Iron overload was inferred indirectly rather than directly measured in mitochondria
    • Did not resolve why neuronal tissues are selectively vulnerable
    • No enzymatic kinetic characterization of mutant protein
  2. 2018 Medium

    Extending FDXR mutations to additional mitochondriopathy patients and mouse brain pathology clarified that CNS damage involves neuroinflammation and gliosis, not solely cell-intrinsic energy failure.

    Evidence Patient genetic analysis plus Fdxr mutant mouse brain histopathology and astrocyte/gliosis immunohistochemistry corroborated by patient autopsy

    PMID:30250212

    Open questions at the time
    • Causal direction between mitochondrial defect and neuroinflammation not dissected
    • Cell-type-specific contributions of gliosis unresolved
  3. 2019 Medium

    Identifying a mitochondrial FDXR-FHIT complex addressed whether FDXR has functions beyond electron transfer, connecting it to oxidative-stress-dependent apoptosis.

    Evidence Protein cross-linking, proteomics, co-IP, and FHIT overexpression in lung cancer cells with ROS/apoptosis readouts

    PMID:30770797

    Open questions at the time
    • Functional consequence of the interaction on FDXR enzymatic activity untested
    • HSP60/HSP10 import role inferred rather than directly demonstrated
    • Single lab; physiological relevance outside cancer cells unknown
  4. 2020 High

    Defining the FDXR→FDX2→IRP2→TP73 axis answered how FDXR loss represses the p73 tumor suppressor, mechanistically coupling iron-sulfur metabolism to a post-transcriptional gene-regulatory circuit.

    Evidence Fdxr/Trp73 mouse models, MEFs, human cancer lines with FDXR knockdown, IRE mutagenesis of TP73 3'UTR, and senescence assays

    PMID:32304229

    Open questions at the time
    • Whether this axis operates in affected neuronal tissues not shown
    • Mechanism by which FDX2 controls IRP2 abundance not fully resolved
  5. 2020 High

    Mouse modeling of a hypomorphic FDXR allele established mitochondrial iron overload and membrane depolarization as the proximate drivers of optic transport defects and neurodegeneration.

    Evidence Fdxr p.Arg389Gln mouse with immunofluorescence, electron microscopy, membrane potential assays, optic transport assays, and histopathology

    PMID:30250212 PMID:32499495

    Open questions at the time
    • Temporal sequence of iron overload versus depolarization not ordered
    • Threshold of residual FDXR activity required for protection unknown
  6. 2020 High

    AAV gene replacement provided causal proof that restoring FDXR expression alone reverses mitochondrial respiratory dysfunction and neuropathy, validating the gene as the disease driver and a therapeutic target.

    Evidence AAV-PHP.B Fdxr cDNA delivery to mutant mice with respiratory chain assays, nerve electron microscopy, and conductivity measurements

    PMID:32995353

    Open questions at the time
    • Durability and dosing thresholds not fully defined
    • Translation to human dosing untested
  7. 2023 Medium

    Linking FDXR to CPT1A-dependent fatty acid oxidation revealed a metabolic role supporting cancer cell growth and endocrine resistance, broadening FDXR function beyond iron metabolism.

    Evidence Metabolomics, RNA microarray, Seahorse FAO assays, and FDXR knockdown in ER+ breast cancer cells

    PMID:37207154

    Open questions at the time
    • Mechanism linking FDXR to CPT1A expression unidentified
    • Single lab and limited to breast cancer context
  8. 2020 Medium

    Demonstrating dose-dependent, multi-variant radiation induction of FDXR transcripts established its utility as a p53-regulated biodosimetry marker.

    Evidence Variant-specific qRT-PCR and full-length nanopore sequencing in radiotherapy patients and in vitro dose-response

    PMID:29330481 PMID:33113898

    Open questions at the time
    • Functional consequence of distinct splice variants on protein activity unknown
    • Transcriptional response not connected to FDXR enzymatic output

Open questions

Synthesis pass · forward-looking unresolved questions
  • How FDXR's enzymatic electron-transfer activity is mechanistically partitioned across its diverse roles—ISC/heme biosynthesis, the IRP2-TP73 circuit, FHIT-dependent apoptosis, and CPT1A-driven fatty acid oxidation—and which functions underlie tissue-specific vulnerability remain unresolved.
  • No structural model of human FDXR or its substrate complexes in the corpus
  • Direct measurement of how mutations alter electron-transfer kinetics lacking
  • Mechanistic link between enzymatic activity and each downstream phenotype not unified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 3 GO:0016740 transferase activity 1
Localization
GO:0005739 mitochondrion 3
Pathway
R-HSA-1430728 Metabolism 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-8953897 Cellular responses to stimuli 2
Partners
FDX2FHIT

Evidence

Reading pass · 9 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2017 Biallelic loss-of-function mutations in FDXR (encoding mitochondrial ferredoxin reductase) cause auditory neuropathy and optic atrophy in humans. Mutant FDXR fibroblasts showed deregulated iron homeostasis and indirect evidence of mitochondrial iron overload. Functional complementation in a yeast strain deleted for ARH1 (the FDXR ortholog) established pathogenicity of the mutations, confirming FDXR's essential role in iron-sulfur cluster (ISC) biosynthesis and heme formation. Whole-exome sequencing of affected families, patient fibroblast iron homeostasis assays, yeast functional complementation of ARH1 deletion American journal of human genetics High 28965846
2019 FDXR physically interacts with the tumor suppressor FHIT within mitochondria. Overexpression of FHIT in FHIT-deficient cancer cells modulates intracellular ROS production (increased ROS after peroxide treatment), leading to increased apoptosis under oxidative stress. The Fhit-FDXR complex was characterized by protein cross-linking and proteomics, and the HSP60/HSP10 chaperonin pair was identified as likely mediating mitochondrial import of FHIT to enable this interaction. Protein cross-linking, proteomics/mass spectrometry, co-immunoprecipitation, overexpression in lung cancer cells with ROS and apoptosis readouts Cell death & disease Medium 30770797
2020 Loss of FDXR increases expression of iron regulatory protein 2 (IRP2) via FDX2, and IRP2 subsequently binds an iron response element (IRE) in the 3'UTR of TP73 mRNA to destabilize it, repressing p73 protein expression. This FDXR→FDX2→IRP2→TP73 axis was established in mouse embryonic fibroblasts and multiple human cancer cell lines. Compound Trp73+/-;Fdxr+/- mice paradoxically lived longer and developed fewer tumors than single heterozygotes, indicating genetic interaction between these two tumor suppressors. Genetically modified mouse models (Fdxr+/- and Trp73+/-), mouse embryonic fibroblasts, human cancer cell lines with FDXR knockdown, IRE mutagenesis in TP73 3'UTR, Western blot, qRT-PCR, senescence assays The Journal of pathology High 32304229
2020 FDXR mutation (p.Arg389Gln hypomorphic) leads to significant optic transport defects, mitochondrial iron overload, and depolarization of the mitochondrial membrane in a mouse model. These changes are associated with neurodegeneration and gliosis in the central nervous system, supporting FDXR's critical role in iron homeostasis as the mechanism underlying FDXR-related neurodegeneration. Fdxr mutant mouse model, immunofluorescence, electron microscopy, mitochondrial membrane potential assay, optic transport assays, brain histopathology Cell death & disease High 30250212 32499495
2018 Biallelic mutations in FDXR cause mitochondriopathy with peripheral neuropathy and optic atrophy in additional patients. Fdxr mutant mouse brain tissues show pathological changes including increased astrocytes, elevated markers of neurodegeneration and gliosis, implicating neuroinflammation as a major factor in FDXR-mediated central neuropathy. Human patient genetic analysis, Fdxr mutant mouse model brain histopathology, immunohistochemistry for astrocyte/gliosis markers, comparison with patient brain autopsy material Journal of human genetics Medium 30250212
2020 AAV-mediated systemic delivery of Fdxr cDNA (using AAV-PHP.B vector) to Fdxr p.Arg389Gln mutant mice restored FDXR protein expression in CNS and peripheral organs, reversed optic atrophy, improved sciatic nerve conductivity, restored mitochondrial respiratory chain complex function, and alleviated sensory neuropathy and neuroinflammation. This demonstrates that restoring FDXR expression is sufficient to rescue the mitochondrial dysfunction phenotype. AAV gene therapy in Fdxr mutant mice, immunofluorescence, Western blot for transduction efficiency, toluidine blue staining, electron microscopy of optic/sciatic nerves, mitochondrial respiratory chain activity assay Molecular therapy. Methods & clinical development High 32995353
2023 FDXR promotes fatty acid oxidation (FAO) in ER+ breast cancer cells by sustaining CPT1A expression. Depletion of FDXR suppressed CPT1A expression and reduced FAO-mediated oxygen consumption rate. Endocrine treatment increased both FDXR and CPT1A expression. Combining FDXR depletion or the FAO inhibitor etomoxir with endocrine therapy synergistically inhibited primary and endocrine-resistant breast cancer cell growth. LC-MS/MS metabolite profiling, RNA microarray, Seahorse XF24 FAO oxygen consumption assay, FDXR knockdown, qPCR, Western blot, MTS/colony formation assays Frontiers in oncology Medium 37207154
2020 Multiple FDXR transcript variants (at least 14 identified) are upregulated in response to ionizing radiation in a dose-dependent manner in human blood in vivo. Nanopore full-length sequencing confirmed high responsiveness of FDXR-201 and FDXR-208 variants; FDXR-218 and FDXR-219 showed no detectable endogenous expression but clear induction after IR. This establishes that FDXR transcriptional radiation response is conserved across multiple splice variants. Quantitative real-time PCR with variant-specific primers, full-length nanopore sequencing, in vivo validation in radiotherapy patients, in vitro IR dose-response International journal of molecular sciences Medium 33113898
2018 FDXR transcription in blood is significantly upregulated in a dose-dependent manner following ionizing radiation exposure in vivo across multiple clinical exposure scenarios (cardiac fluoroscopy, CT, radiotherapy). No significant differences were found between ex vivo and in vivo samples. Gender, infection status, and antioxidants only moderately affect FDXR transcription. This establishes FDXR as a p53-regulated radiation-responsive gene that can be used for biological dosimetry. RT-qPCR of FDXR mRNA in patient blood samples from multiple radiation exposure cohorts, in vivo dose-response analysis Scientific reports Medium 29330481

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1983 Cloning and structural analyses of hepatitis B virus DNAs, subtype adr. Nucleic acids research 318 6306594
1984 Complete nucleotide sequence of hepatitis B virus DNA of subtype adr and its conserved gene organization. Gene 196 6510717
2018 FDXR is a biomarker of radiation exposure in vivo. Scientific reports 104 29330481
2005 Overexpression and significance of prion protein in gastric cancer and multidrug-resistant gastric carcinoma cell line SGC7901/ADR. International journal of cancer 95 15386405
2000 bcl-2 over-expression enhances NF-kappaB activity and induces mmp-9 transcription in human MCF7(ADR) breast-cancer cells. International journal of cancer 95 10738245
1997 Expression of the mutated p53 tumor suppressor protein and its molecular and biochemical characterization in multidrug resistant MCF-7/Adr human breast cancer cells. Oncogene 87 9053847
1999 Negative regulation of MDR1 promoter activity in MCF-7, but not in multidrug resistant MCF-7/Adr, cells by cross-coupled NF-kappa B/p65 and c-Fos transcription factors and their interaction with the CAAT region. Biochemistry 83 10026303
2010 Molecular mechanism of suppression of MDR1 by puerarin from Pueraria lobata via NF-kappaB pathway and cAMP-responsive element transcriptional activity-dependent up-regulation of AMP-activated protein kinase in breast cancer MCF-7/adr cells. Molecular nutrition & food research 72 20077420
2017 FDXR Mutations Cause Sensorial Neuropathies and Expand the Spectrum of Mitochondrial Fe-S-Synthesis Diseases. American journal of human genetics 71 28965846
2014 The dsRBP and inactive editor ADR-1 utilizes dsRNA binding to regulate A-to-I RNA editing across the C. elegans transcriptome. Cell reports 66 24508457
2004 Ceramide reduction and transcriptional up-regulation of glucosylceramide synthase through doxorubicin-activated Sp1 in drug-resistant HL-60/ADR cells. Cancer research 65 15342415
2014 Novel nanostructured lipid carrier co-loaded with doxorubicin and docosahexaenoic acid demonstrates enhanced in vitro activity and overcomes drug resistance in MCF-7/Adr cells. Pharmaceutical research 63 24522814
2002 Modulation of multidrug resistance by artemisinin, artesunate and dihydroartemisinin in K562/adr and GLC4/adr resistant cell lines. Biological & pharmaceutical bulletin 62 12499639
2017 Metformin synergistically suppress tumor growth with doxorubicin and reverse drug resistance by inhibiting the expression and function of P-glycoprotein in MCF7/ADR cells and xenograft models. Oncotarget 60 29416762
1996 Comparison of staurosporine and four analogues: their effects on growth, rhodamine 123 retention and binding to P-glycoprotein in multidrug-resistant MCF-7/Adr cells. British journal of cancer 58 8624264
2015 Cucurbitacin D induces cell cycle arrest and apoptosis by inhibiting STAT3 and NF-κB signaling in doxorubicin-resistant human breast carcinoma (MCF7/ADR) cells. Molecular and cellular biochemistry 57 26169986
2010 Differential chemosensitization of P-glycoprotein overexpressing K562/Adr cells by withaferin A and Siamois polyphenols. Molecular cancer 56 20438634
2015 A smart tumor targeting peptide-drug conjugate, pHLIP-SS-DOX: synthesis and cellular uptake on MCF-7 and MCF-7/Adr cells. Drug delivery 50 25853477
1992 Protein kinase C isoforms in multidrug resistant P388/ADR cells: a possible role in daunorubicin transport. Cancer letters 50 1347251
2018 Matrine reversed multidrug resistance of breast cancer MCF-7/ADR cells through PI3K/AKT signaling pathway. Journal of cellular biochemistry 49 29130495
2014 Cabozantinib reverses multidrug resistance of human hepatoma HepG2/adr cells by modulating the function of P-glycoprotein. Liver international : official journal of the International Association for the Study of the Liver 49 24621440
2004 Gene-gene interaction between PPAR gamma 2 and ADR beta 3 increases obesity risk in children and adolescents. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity 48 15543217
2019 Fhit-Fdxr interaction in the mitochondria: modulation of reactive oxygen species generation and apoptosis in cancer cells. Cell death & disease 47 30770797
2007 Tumor inhibitory effect of gefitinib (ZD1839, Iressa) and taxane combination therapy in EGFR-overexpressing breast cancer cell lines (MCF7/ADR, MDA-MB-231). International journal of cancer 47 17036319
2009 Estradiol and progesterone-mediated regulation of P-gp in P-gp overexpressing cells (NCI-ADR-RES) and placental cells (JAR). Molecular pharmaceutics 45 19813763
2019 Involvement of the PI3K/Akt/Nrf2 Signaling Pathway in Resveratrol-Mediated Reversal of Drug Resistance in HL-60/ADR Cells. Nutrition and cancer 42 31032633
2017 Targeting P-glycoprotein and SORCIN: Dihydromyricetin strengthens anti-proliferative efficiency of adriamycin via MAPK/ERK and Ca2+ -mediated apoptosis pathways in MCF-7/ADR and K562/ADR. Journal of cellular physiology 42 28681913
2016 Enhanced Cytotoxicity of Folic Acid-Targeted Liposomes Co-Loaded with C6 Ceramide and Doxorubicin: In Vitro Evaluation on HeLa, A2780-ADR, and H69-AR Cells. Molecular pharmaceutics 40 26702994
2019 [EGFR-TKI ADR Management Chinese Expert Consensus]. Zhongguo fei ai za zhi = Chinese journal of lung cancer 39 30827323
2016 Chaetominine reduces MRP1-mediated drug resistance via inhibiting PI3K/Akt/Nrf2 signaling pathway in K562/Adr human leukemia cells. Biochemical and biophysical research communications 39 27038543
2010 MCF-7/ADR cells (re-designated NCI/ADR-RES) are not derived from MCF-7 breast cancer cells: a loss for breast cancer multidrug-resistant research. Medical oncology (Northwood, London, England) 37 21116879
2016 Genomic and transcriptomic profiling of resistant CEM/ADR-5000 and sensitive CCRF-CEM leukaemia cells for unravelling the full complexity of multi-factorial multidrug resistance. Scientific reports 35 27824156
2020 Integrated analysis of the molecular pathogenesis of FDXR-associated disease. Cell death & disease 34 32499495
2014 Psammaplin A induces Sirtuin 1-dependent autophagic cell death in doxorubicin-resistant MCF-7/adr human breast cancer cells and xenografts. Biochimica et biophysica acta 34 25445714
2003 Down-regulation of survivin expression reversed multidrug resistance in adriamycin-resistant HL-60/ADR cell line. Acta pharmacologica Sinica 34 14653950
2020 FDXR regulates TP73 tumor suppressor via IRP2 to modulate aging and tumor suppression. The Journal of pathology 33 32304229
2013 Oroxylin A reverses P-glycoprotein-mediated multidrug resistance of MCF7/ADR cells by G2/M arrest. Toxicology letters 33 23470866
2012 The EU-ADR Web Platform: delivering advanced pharmacovigilance tools. Pharmacoepidemiology and drug safety 33 23208789
2018 Biallelic mutations in FDXR cause neurodegeneration associated with inflammation. Journal of human genetics 32 30250212
2016 Psoralen reverses the P-glycoprotein-mediated multidrug resistance in human breast cancer MCF-7/ADR cells. Molecular medicine reports 30 27082231
2016 Dioscin strengthens the efficiency of adriamycin in MCF-7 and MCF-7/ADR cells through autophagy induction: More than just down-regulation of MDR1. Scientific reports 30 27329817
2006 Nitric oxide synthase expressions in ADR-induced cardiomyopathy in rats. Journal of biochemistry and molecular biology 30 17129413
2020 In Vivo Validation of Alternative FDXR Transcripts in Human Blood in Response to Ionizing Radiation. International journal of molecular sciences 29 33113898
2016 Salubrinal-Mediated Upregulation of eIF2α Phosphorylation Increases Doxorubicin Sensitivity in MCF-7/ADR Cells. Molecules and cells 29 26743901
1993 Effect of staurosporine derivatives on protein kinase activity and vinblastine accumulation in mouse leukaemia P388/ADR cells. The Journal of pharmacy and pharmacology 29 8094445
2012 Baicalin induces apoptosis in leukemia HL-60/ADR cells via possible down-regulation of the PI3K/Akt signaling pathway. Asian Pacific journal of cancer prevention : APJCP 26 22799292
2005 Beta2-ADR haplotypes/polymorphisms associate with bronchodilator response and total IgE in grass allergy. Allergy 26 16197474
2016 Knockdown of SALL4 inhibits the proliferation and reverses the resistance of MCF-7/ADR cells to doxorubicin hydrochloride. BMC molecular biology 24 26935744
2018 Paris saponin VII induces cell cycle arrest and apoptosis by regulating Akt/MAPK pathway and inhibition of P-glycoprotein in K562/ADR cells. Phytotherapy research : PTR 23 29377384
2016 Reversal of multidrug resistance in breast cancer MCF-7/ADR cells by h-R3-siMDR1-PAMAM complexes. International journal of pharmaceutics 23 27444552
1992 Comparative effects of protein phosphatase inhibitors (okadaic acid and calyculin A) on human leukemia HL60, HL60/ADR and K562 cells. Biochemical and biophysical research communications 23 1325792
2003 Down-regulation of Raf-1 kinase is associated with paclitaxel resistance in human breast cancer MCF-7/Adr cells. Cancer letters 22 12691824
2024 Design, synthesis, and bioactivity evaluation of novel indole-selenide derivatives as P-glycoprotein inhibitors against multi-drug resistance in MCF-7/ADR cell. European journal of medicinal chemistry 21 38364715
2023 Design, synthesis and biological evaluation of novel phenylfuran-bisamide derivatives as P-glycoprotein inhibitors against multidrug resistance in MCF-7/ADR cell. European journal of medicinal chemistry 21 36645980
2021 The effects and mechanisms of aloe-emodin on reversing adriamycin-induced resistance of MCF-7/ADR cells. Phytotherapy research : PTR 21 33792091
2018 Gambogenic acid reverses P-glycoprotein mediated multidrug resistance in HepG2/Adr cells and its underlying mechanism. Biochemical and biophysical research communications 21 30538042
2015 Chabamide induces cell cycle arrest and apoptosis by the Akt/MAPK pathway and inhibition of P-glycoprotein in K562/ADR cells. Anti-cancer drugs 21 25714087
2022 Novel Hybrids of 3-Substituted Coumarin and Phenylsulfonylfuroxan as Potent Antitumor Agents with Collateral Sensitivity against MCF-7/ADR. Journal of medicinal chemistry 20 35737669
2021 Grape seed proanthocyanidin extract induces apoptosis of HL-60/ADR cells via the Bax/Bcl-2 caspase-3/9 signaling pathway. Translational cancer research 20 35116693
2020 Suaeda vermiculata Aqueous-Ethanolic Extract-Based Mitigation of CCl4-Induced Hepatotoxicity in Rats, and HepG-2 and HepG-2/ADR Cell-Lines-Based Cytotoxicity Evaluations. Plants (Basel, Switzerland) 20 33003604
2018 Reverse Multidrug Resistance in Human HepG2/ADR by Anti-miR-21 Combined with Hyperthermia Mediated by Functionalized Gold Nanocages. Molecular pharmaceutics 20 29966415
2018 Targeting P-Glycoprotein: Nelfinavir Reverses Adriamycin Resistance in K562/ADR Cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 20 30497065
2020 Arborinine, a potential LSD1 inhibitor, inhibits epithelial-mesenchymal transition of SGC-7901 cells and adriamycin-resistant gastric cancer SGC-7901/ADR cells. Investigational new drugs 19 33215324
2018 Combination of dihydromyricetin and ondansetron strengthens antiproliferative efficiency of adriamycin in K562/ADR through downregulation of SORCIN: A new strategy of inhibiting P-glycoprotein. Journal of cellular physiology 19 30171603
2015 Pseudolaric acid B circumvents multidrug resistance phenotype in human gastric cancer SGC7901/ADR cells by downregulating Cox-2 and P-gp expression. Cell biochemistry and biophysics 19 25077681
2015 Comparison of cell membrane damage induced by the therapeutic ultrasound on human breast cancer MCF-7 and MCF-7/ADR cells. Ultrasonics sonochemistry 19 25771334
2012 Zona occludens-2 protects against podocyte dysfunction induced by ADR in mice. American journal of physiology. Renal physiology 19 23034938
2020 A quantitative N-glycoproteomics study of cell-surface N-glycoprotein markers of MCF-7/ADR cancer stem cells. Analytical and bioanalytical chemistry 18 32030495
2019 Peptidylarginine deiminase 4 overexpression resensitizes MCF-7/ADR breast cancer cells to adriamycin via GSK3β/p53 activation. Cancer management and research 18 30666159
2019 Artemisinin-indole and artemisinin-imidazole hybrids: Synthesis, cytotoxic evaluation and reversal effects on multidrug resistance in MCF-7/ADR cells. Bioorganic & medicinal chemistry letters 18 30837097
2017 The effect of saikosaponin D on doxorubicin pharmacokinetics and its MDR reversal in MCF-7/adr cell xenografts. European review for medical and pharmacological sciences 18 29077148
2013 Reversal effect of rosmarinic acid on multidrug resistance in SGC7901/Adr cell. Journal of Asian natural products research 18 23421517
2018 Paris saponin VII reverses chemoresistance in breast MCF-7/ADR cells. Journal of ethnopharmacology 17 30552993
2017 Pharmacokinetics of the Cardioprotective Drug Dexrazoxane and Its Active Metabolite ADR-925 with Focus on Cardiomyocytes and the Heart. The Journal of pharmacology and experimental therapeutics 17 29273587
2023 FDXR drives primary and endocrine-resistant tumor cell growth in ER+ breast cancer via CPT1A-mediated fatty acid oxidation. Frontiers in oncology 16 37207154
2021 Co-Inhibition of P-gp and Hsp90 by an Isatin-Derived Compound Contributes to the Increase of the Chemosensitivity of MCF7/ADR-Resistant Cells to Doxorubicin. Molecules (Basel, Switzerland) 15 35011321
2020 Shenmai injection suppresses multidrug resistance in MCF-7/ADR cells through the MAPK/NF-κB signalling pathway. Pharmaceutical biology 15 32251615
2012 Transport, metabolism, cytotoxicity and effects of novel taxanes on the cell cycle in MDA-MB-435 and NCI/ADR-RES cells. Naunyn-Schmiedeberg's archives of pharmacology 15 22855252
2011 CIAPIN1 confers multidrug resistance through up-regulation of MDR-1 and Bcl-L in LoVo/Adr cells and is independent of p53. Oncology reports 15 21240465
2023 Cyperotundone combined with adriamycin induces apoptosis in MCF-7 and MCF-7/ADR cancer cells by ROS generation and NRF2/ARE signaling pathway. Scientific reports 14 36697441
2013 Network characteristic analysis of ADR-related proteins and identification of ADR-ADR associations. Scientific reports 14 23625301
2018 In vitro anti-leukemia activity of dual PI3K/mTOR inhibitor Voxtalisib on HL60 and K562 cells, as well as their multidrug resistance counterparts HL60/ADR and K562/A02 cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 13 29710665
1991 Analgesic effects of S and R isomers of the novel 5-HT3 receptor antagonists ADR-851 and ADR-882 in rats. European journal of pharmacology 13 1804661
1986 Cloning and analysis of integrated hepatitis B virus DNA of the adr subtype derived from a human primary liver cell carcinoma. The Journal of general virology 13 3007665
2023 Cytotoxic and chemomodulatory effects of Phyllanthus niruri in MCF-7 and MCF-7ADR breast cancer cells. Scientific reports 12 36792619
2021 Report of a case with ferredoxin reductase (FDXR) gene variants in a Chinese boy exhibiting hearing loss, visual impairment, and motor retardation. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience 12 33742450
2021 CIP2A silencing alleviates doxorubicin resistance in MCF7/ADR cells through activating PP2A and autophagy. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 12 33948919
2021 Astragalus IV Undermines Multi-Drug Resistance and Glycolysis of MDA-MB-231/ADR Cell Line by Depressing hsa_circ_0001982-miR-206/miR-613 Axis. Cancer management and research 12 34326666
2019 Paris saponin VII enhanced the sensitivity of HepG2/ADR cells to ADR via modulation of PI3K/AKT/MAPK signaling pathway. The Kaohsiung journal of medical sciences 12 31688993
2018 Acid-breakable TPGS-functionalized and diallyl disulfide-crosslinked nanogels for enhanced inhibition of MCF-7/ADR solid tumours. Journal of materials chemistry. B 12 32254549
2017 Antiproliferative effect of ZSTK474 alone or in combination with chemotherapeutic drugs on HL60 and HL60/ADR cells. Oncotarget 12 28388564
2023 Discovery of 2,5-disubstituted furan derivatives featuring a benzamide motif for overcoming P-glycoprotein mediated multidrug resistance in MCF-7/ADR cell. European journal of medicinal chemistry 11 37229830
2023 In Vitro Cytotoxic Study of Euphorbia grantii Oliv. Aerial Parts against MCF-7 and MCF-7ADR Breast Cancer Cell Lines: A Bioactivity-Guided Isolation. ACS omega 11 37251150
2020 Systemic Delivery of AAV-Fdxr Mitigates the Phenotypes of Mitochondrial Disorders in Fdxr Mutant Mice. Molecular therapy. Methods & clinical development 11 32995353
2020 Puerarin sensitized K562/ADR cells by inhibiting NF-κB pathway and inducing autophagy. Phytotherapy research : PTR 11 33141989
2023 Identification of co-regulated genes associated with doxorubicin resistance in the MCF-7/ADR cancer cell line. Frontiers in oncology 10 37397367
2021 Investigating ADR mechanisms with Explainable AI: a feasibility study with knowledge graph mining. BMC medical informatics and decision making 10 34039343
2021 A 4-Gene Signature of CDKN1, FDXR, SESN1 and PCNA Radiation Biomarkers for Prediction of Patient Radiosensitivity. International journal of molecular sciences 10 34638945
2017 Tuberostemonine reverses multidrug resistance in chronic myelogenous leukemia cells K562/ADR. Journal of Cancer 10 28529625
2013 Reversal effects of Rabdosia rubescens extract on multidrug resistance of MCF-7/Adr cells in vitro. Pharmaceutical biology 10 23777360

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