ArticlePloS one2017
Transcriptional activation of HIF-1 by a ROS-ERK axis underlies the resistance to photodynamic therapy.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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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
35 citing papers in PubMed, 64 citations in OpenAlex.
- Photodynamic therapy in head and neck squamous cell carcinoma: immunomodulation and stromal targeting of cancer-associated fibroblasts.Translational oncology · 2026Review
- Neuroprotective effects of agomelatine in a D-galactose-induced hippocampal aging model.Toxicology reports · 2026Article
- Photodynamic Therapy Combined with Anticancer Drug Therapy in the Treatment of Malignant Neoplasms.Cells · 2026Review
- Implementing Photodynamic Therapy to Activate the IFN-1 Pathway in Melanoma Cells: A Protocol for Inducing Immunogenic Cell Death and Enhancing Dendritic Cell Maturation.Methods in molecular biology (Clifton, N.J.) · 2026Article
- From Carcinogenesis to Drug Resistance: The Multifaceted Role of Oxidative Stress in Head and Neck Cancer.Cancers · 2025Review
- Formulation Strategies for Immunomodulatory Natural Products in 3D Tumor Spheroids and Organoids: Current Challenges and Emerging Solutions.Pharmaceutics · 2025Review
- Understanding chronic inflammation: couplings between cytokines, ROS, NO, CaFrontiers in immunology · 2025Review
- Erlotinib Improves the Response of Glioblastoma Cells Resistant to Photodynamic Therapy.Brain sciences · 2024Article
- Molecular Determinants for Photodynamic Therapy Resistance and Improved Photosensitizer Delivery in Glioma.International journal of molecular sciences · 2024Review
- Cellular memory function from 3D to 2D: Three-dimensional high density collagen microfiber cultures induce their resistance to reactive oxygen species.Materials today. Bio · 2024Article
- Review
- Photodynamic therapy in cancer stem cells - state of the art.Lasers in medical science · 2023Review
- Article
- Article
- The signaling pathway of hypoxia inducible factor in regulating gut homeostasis.Frontiers in microbiology · 2023Review
- Photodynamic Therapy for Inflammatory and Cancerous Diseases of the Intestines: Molecular Mechanisms and Prospects for Application.International journal of biological sciences · 2023Review
- Reactive Oxygen Species in Modulating Intestinal Stem Cell Dynamics and Function.Stem cell reviews and reports · 2022Review
- Hypoxia signaling in human health and diseases: implications and prospects for therapeutics.Signal transduction and targeted therapy · 2022Review
- Iron commensalism of mesenchymal glioblastoma promotes ferroptosis susceptibility upon dopamine treatment.Communications biology · 2022Article
- Intraperitoneal Triamcinolone Reduces Postoperative Adhesions, Possibly through Alteration of Mitochondrial Function.Journal of clinical medicine · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Photodynamic therapy (PDT), a promising treatment option for cancer, involves the activation of a photosensitizer (PS) by local irradiation with visible light. Excitation of the PS leads to a series of photochemical reactions and consequently the local generation of harmful reactive oxygen species (ROS) causing limited or none systemic defects. However, the development of resistance to this promising therapy has slowed down its translation into the clinical practice. Thus, there is an increase need in understanding of the molecular mechanism underlying resistance to PDT. Here, we aimed to examine whether a relationship exists between PDT outcome and ROS-involvement in the resistance mechanism in photosensitized cancer cells. In order to recapitulate tumor architecture of the respective original tumor, we developed a multicellular three-dimensional spheroid system comprising a normoxic periphery, surrounding a hypoxic core. Using Me-ALA, a prodrug of the PS PpIX, in human colorectal spheroids we demonstrate that HIF-1 transcriptional activity was strongly up-regulated and mediates PDT resistant phenotype. RNAi knockdown of HIF-1 impairs resistance to PDT. Oxidative stress-mediated activation of ERK1/2 followed PDT was involved on positive modulation of HIF-1 transcriptional activity after photodynamic treatment. ROS scavenging and MEK/ERK pathway inhibition abrogated the PDT-mediated HIF-1 upregulation. Together our data demonstrate that resistance to PDT is in part mediated by the activation of a ROS-ERK1/2-HIF-1 axis, thus, identifying novel therapeutic targets that could be used in combination with PDT.
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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.