ArticleScientific reports2023
Nrf2 inhibition increases sensitivity to chemotherapy of colorectal cancer by promoting ferroptosis and pyroptosis.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 58 citations in OpenAlex.
- Rewiring redox defense: Nrf2-driven antioxidant signaling as a gateway to programmed cell death activation in colorectal cancer.Genes & diseases · 2027Review
- Gut microbiota-derived metabolites as context-dependent modulators of Nrf2 signaling in inflammation-driven carcinogenesis.Gut microbes · 2026Review
- Translating the Crosstalk Between Unfolded Protein Response and Ferroptosis to Cancer Therapies.Current oncology reports · 2026Review
- Itaconate and its derivatives in human health and diseases.Signal transduction and targeted therapy · 2026Review
- Lipid peroxidation in cancer: a double-edged sword shaping progression and therapy.Medical oncology (Northwood, London, England) · 2026Review
- AI-Guided Ferroptosis Biomarker Discovery and Routine Laboratory-Based Machine Learning for Predicting Nodal Metastasis in Colon Cancer.Metabolites · 2026Article
- Iron Metabolism in the Colorectal Tumor Microenvironment: From Preneoplastic Lesions to Cancer Progression.International journal of molecular sciences · 2026Review
- Role of itaconate in intestinal disease (Review).International journal of molecular medicine · 2026Review
- The role of NRF2 in human cancers: Pre-clinical insights paving the way for clinical trials.Journal of pharmaceutical analysis · 2026Review
- Pyroptosis as a double-edged sword in colorectal cancer: Molecular mechanisms and therapeutic opportunities.Apoptosis : an international journal on programmed cell death · 2026Review
- Ferroptosis as a therapeutic target in cancer: mechanisms, immune interactions, and emerging strategies.Molecular cancer · 2026Review
- Targeting cell death: a promising approach for colorectal cancer therapy.Cancer cell international · 2026Review
- Next-Generation Redox Mediators: Itaconate, Nitro-Fatty Acids, Reactive Sulfur Species and Succinate as Emerging Switches in Predictive Redox Medicine.Antioxidants (Basel, Switzerland) · 2026Review
- Oxidative Stress and Inflammation in Colorectal Cancer-Redox-Immune Crosstalk, Biomarkers, and Translational Implications: A Qualitative Systematic Review.Life (Basel, Switzerland) · 2026Review
- Autophagy regulation of pyroptosis and ferroptosis: a new strategy for colorectal cancer treatment.Apoptosis : an international journal on programmed cell death · 2026Review
- The dual roles of ferroptosis in digestive tract tumors: mechanisms, microenvironment regulation, and therapeutic integration with emphasis on immune interactions.Frontiers in immunology · 2026Review
- The mechanism of Akkermansia muciniphila inhibiting the proliferation of colorectal cancer cells via ferroptosis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Identification of Drug-resistant Cell Subpopulations in Colorectal Cancer Through Single-cell Analysis and Exploration of Potential Therapeutic Strategies.Current medicinal chemistry · 2026Article
- Caspase-8 expression and its Src dependent phosphorylation on Tyrosine 380 triggers NRF2 signaling activation in glioblastoma.Cell death and differentiation · 2025Article
- Pyroptosis in cancer therapy: a double-edged sword for immune activation and tumor progression.Molecular cancer · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxaliplatin is widely used in chemotherapy for colorectal cancer (CRC), but its sensitivity has become a major obstacle to limiting efficacy. Many literatures reported that Nrf2 activation promoted tumor chemoresistance. In this study, we explored the role and mechanism of Nrf2 inhibition in oxaliplatin-based chemosensitivity of CRC. In vitro experiments, we applied 4-octyl itaconate (4-OI) to activate Nrf2, and used lentivirus to knock down Nrf2 in CRC cell lines. By measuring cell viability, colony formation, apoptosis, reactive oxygen species production, and western blot, we found that oxaliplatin and lobaplatin suppressed the growth of HCT-116 and LOVO cells in a dose-dependent manner, and promoted the expression of Nrf2. 4-OI, an Nrf2 activator, reduced the sensibility of CRC cells to oxaliplatin and lobaplatin, while the knockdown of Nrf2 promoted the sensibility of CRC cells to oxaliplatin and lobaplatin. Through the public databases, we found that the expression of GPX4 in normal tissues was lower compared with cancer tissues in CRC, and the high GPX4 expression predicted a poor prognosis. Meanwhile, we found that oxaliplatin reduced the expression of GPX4 in vitro. The knockdown of Nrf2 enhanced the effects of oxaliplatin to reduce the expression of GPX4 and GSH content, and increase the MDA content, which enhanced oxaliplatin-induced ferroptosis. Subsequently, we found that oxaliplatin promoted the expression of GSDME-N, and induced LDH, IL-1β, and TNF-a release, and the knockdown of Nrf2 aggravated the occurrence of GSMDE-mediated pyroptosis. Finally, we found that the knockdown of Nrf2 enhanced the inhibition of oxaliplatin on HCT116 xenograft tumor growth in vivo. Thus, our study showed that Nrf2 inhibition improved sensitivity to oxaliplatin of CRC cells by promoting ferroptosis and pyroptosis, which provided a new target for overcoming chemoresistance in CRC.
Indexed as
Identifiers
What OpenQuestion holds
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.