ArticleJournal of experimental & clinical cancer research : CR2018
Increasing intratumor C/EBP-β LIP and nitric oxide levels overcome resistance to doxorubicin in triple negative breast cancer.
Article in Journal of experimental & clinical cancer research : CR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Meta analysis of bioactive compounds, miRNA, siRNA and cell death regulators as sensitizers to doxorubicin induced chemoresistance.Apoptosis : an international journal on programmed cell death · 2022Pooled it
- Beyond conventional therapies: the evolution of targeted agents and immunotherapies in triple-negative breast cancer.Acta pharmacologica Sinica · 2026Review
- Article
- A PRK-armed oncolytic adenovirus drives calreticulin exposure for dendritic cell licensing to prime antitumor CD8⁺ T cells and synergizes with anti-PD-1 or CAR-T therapy in colorectal cancer.Journal of gastroenterology · 2026Article
- Chemoimmunomodulation in triple negative breast cancer: a key to maximizing anti-PD-1 chemoimmunotherapeutic efficacy.Oncoimmunology · 2025Review
- Doxorubicin Effects Breast Cancer Proliferation via the NEAT1/miR-410-3p Axis.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- Role of Hypoxia-Associated Long Noncoding RNAs in Cancer Chemo-Therapy Resistance.International journal of molecular sciences · 2025Review
- Exploring TNFR1: from discovery to targeted therapy development.Journal of translational medicine · 2025Review
- The Landscape of Potential Targeted Treatments and Chemotherapy Efficacy Biomarkers for TNBC.Breast cancer (Dove Medical Press) · 2025Review
- Ecteinascidin synthetic analogues: a new class of selective inhibitors of transcription, exerting immunogenic cell death in refractory malignant pleural mesothelioma.Journal of experimental & clinical cancer research : CR · 2024Article
- TFEB controls sensitivity to chemotherapy and immuno-killing in non-small cell lung cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- Unveiling the mechanisms and challenges of cancer drug resistance.Cell communication and signaling : CCS · 2024Review
- Use of Enzymatically Activated Carbon Monoxide Donors for Sensitizing Drug-Resistant Tumor Cells.International journal of molecular sciences · 2023Article
- In Vitro Anticancer Activity of Methanolic Extract ofMolecules (Basel, Switzerland) · 2022Article
- Naked and Decorated Nanoparticles Containing HInternational journal of molecular sciences · 2022Article
- Mitochondrial ROS drive resistance to chemotherapy and immune-killing in hypoxic non-small cell lung cancer.Journal of experimental & clinical cancer research : CR · 2022Article
- Gasotransmitters in the tumor microenvironment: Impacts on cancer chemotherapy (Review).Molecular medicine reports · 2022Review
- [Effectiveness of TRB3 on human hepatocellular carcinoma cells proliferation, apoptosis and migration].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2021Article
- Role of ABCB1 in mediating chemoresistance of triple-negative breast cancers.Bioscience reports · 2021Review
- Overcoming Chemoresistance: Altering pH of Cellular Compartments by Chloroquine and Hydroxychloroquine.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundTriple negative breast cancer (TNBC) easily develops resistance to the first-line drug doxorubicin, because of the high levels of the drug efflux transporter P-glycoprotein (Pgp) and the activation of pro-survival pathways dependent on endoplasmic reticulum (ER). Interfering with these mechanisms may overcome the resistance to doxorubicin, a still unmet need in TNBC.
methodsWe analyzed a panel of human and murine breast cancer cells for their resistance to doxorubicin, Pgp expression, lysosome and proteasome activity, nitrite production, ER-dependent cell death and immunogenic cell death parameters. We evaluated the efficacy of genetic (C/EBP-β LIP induction) and pharmacological strategies (lysosome and proteasome inhibitors), in restoring the ER-dependent and immunogenic-dependent cell death induced by doxorubicin, in vitro and in syngeneic mice bearing chemoresistant TNBC. The results were analyzed by one-way analysis of variance test.
resultsWe found that TNBC cells characterized by high levels of Pgp and resistance to doxorubicin, had low induction of the ER-dependent pro-apoptotic factor C/EBP-β LIP upon doxorubicin treatment and high activities of lysosome and proteasome that constitutively destroyed LIP. The combination of chloroquine and bortezomib restored doxorubicin sensitivity by activating multiple and interconnected mechanisms. First, chloroquine and bortezomib prevented C/EBP-β LIP degradation and activated LIP-dependent CHOP/TRB3/caspase 3 axis in response to doxorubicin. Second, C/EBP-β LIP down-regulated Pgp and up-regulated calreticulin that triggered the dendritic cell (DC)-mediated phagocytosis of tumor cell, followed by the activation of anti-tumor CD8
conclusionsWe suggest that preventing C/EBP-β LIP degradation by lysosome and proteasome inhibitors triggers multiple virtuous circuitries that restore ER-dependent apoptosis, down-regulate Pgp and re-activate the DC/CD8
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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 OpenQuestion graph.