ArticleOncogene2020
Metabolic targeting of HIF-1α potentiates the therapeutic efficacy of oxaliplatin in colorectal cancer.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 79 citations in OpenAlex.
- Translational insights and clinical challenges of targeting cancer stem cells.Signal transduction and targeted therapy · 2026Review
- Cancer stem cell-driven drug resistance in colorectal carcinoma: molecular aspects and therapeutic potentials.Molecular cancer · 2026Review
- Serine-arginine protein kinase 1 (SRPK1) is under-expressed in mucinous colorectal cancer, and may mediate resistance to oxaliplatin.The pharmacogenomics journal · 2025Article
- Crosstalk Between Metabolic Reprogramming and Epigenetic Modifications in Colorectal Cancer: Mechanisms and Clinical Applications.Current issues in molecular biology · 2025Review
- Crosstalk between cancer‑associated fibroblasts and inflammation in tumor microenvironment: A novel perspective in cancer therapy (Review).Oncology reports · 2025Review
- Multi-parameter magnetic resonance imaging of zebularine in liver fibrosis treatment and calcineurin/World journal of gastroenterology · 2025Article
- Decoding the hypoxic tumor microenvironment in colorectal cancer for prognostic modeling and therapeutic target discovery.Frontiers in immunology · 2025Article
- Integrating network pharmacology and computational biology to propose Yiqi Sanjie formula's mechanisms in treating NSCLC: molecular docking, ADMET, and molecular dynamics simulation.Translational cancer research · 2024Article
- The Role of Adipocytes Recruited as Part of Tumor Microenvironment in Promoting Colorectal Cancer Metastases.International journal of molecular sciences · 2024Review
- Changes in the Expression of Genes Regulating the Response to Hypoxia, Inflammation, Cell Cycle, Apoptosis, and Epithelial Barrier Functioning during Colitis-Associated Colorectal Cancer Depend on Individual Hypoxia Tolerance.International journal of molecular sciences · 2024Article
- Novel hypoxia- and lactate metabolism-related molecular subtyping and prognostic signature for colorectal cancer.Journal of translational medicine · 2024Article
- Targeting key RNA methylation enzymes to improve the outcome of colorectal cancer chemotherapy (Review).International journal of oncology · 2024Review
- Human colorectal cancer: upregulation of the adaptor protein Rai in TILs leads to cell dysfunction by sustaining GSK-3 activation and PD-1 expression.Cancer immunology, immunotherapy : CII · 2024Article
- Thymosin α1 combined with XELOX improves immune function and reduces serum tumor markers in colorectal cancer patients after radical surgery.Open life sciences · 2024Article
- Semisynthesis and anti-cancer properties of novel honokiol derivatives in human nasopharyngeal carcinoma CNE-2Z cells.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Article
- Pharmacologic Ascorbate and DNMT Inhibitors Increase DUOX Expression and Peroxide-Mediated Toxicity in Pancreatic Cancer.Antioxidants (Basel, Switzerland) · 2023Article
- USP10 Contributes to Colon Carcinogenesis via mTOR/S6K Mediated HIF-1α but Not HIF-2α Protein Synthesis.Cells · 2023Article
- The Epithelial to Mesenchymal Transition in Colorectal Cancer Progression: The Emerging Role of Succinate Dehydrogenase Alterations and Succinate Accumulation.Biomedicines · 2023Review
- Long non‑coding RNA LINC00460 contributes as a potential prognostic biomarker through its oncogenic role with ANXA2 in colorectal polyps.Molecular biology reports · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug resistance is a major problem limiting the efficacy of chemotherapy in cancer treatment, and the hypoxia-induced stabilization of HIF-1α plays a role in this process. HIF-1α overexpression has been observed in a variety of human cancers, including colorectal cancer (CRC). Therefore, targeting HIF-1α is a promising strategy for overcoming chemoresistance to enhance the efficacy of chemotherapies in CRC. Here, we show that DNMT inhibitors can induce HIF-1α degradation to overcome oxaliplatin resistance and enhance anti-CRC therapy. We found that a low-toxicity DNMT inhibitor, zebularine, could downregulate HIF-1α expression and overcome hypoxia-induced oxaliplatin resistance in HCT116 cells and showed efficacy in HCT116 xenograft models and AOM/DSS-induced CRC mouse models. Zebularine could induce the degradation of HIF-1α protein through hydroxylation. LC-MS analysis showed a decrease in succinate in various CRC cells under hypoxia and in colon tissues of AOM/DSS-induced CRC mice. The decrease was reversed by zebularine. Tumor angiogenesis was also reduced by zebularine. Furthermore, zebularine potentiated the anticancer effect of oxaliplatin in AOM/DSS-induced CRC models. This finding provides a new strategy in which an increase in HIF-1α hydroxylation could overcome oxaliplatin resistance to enhance anti-CRC therapy.
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