ArticleOncotarget2016
Inhibition of hypoxia inducible factor 1 and topoisomerase with acriflavine sensitizes perihilar cholangiocarcinomas to photodynamic therapy.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 62 citations in OpenAlex.
- Overcoming Photodynamic Therapy Resistance: GSH-Responsive AIE Photosensitizer-Hydroxycamptothecin Nanoliposomes for Extrahepatic Cholangiocarcinoma.Advanced healthcare materials · 2026Article
- HIF inhibition: Current strategies and clinical challenges.Redox biology · 2026Review
- Biomimetic Tumour Model Systems for Pancreatic Ductal Adenocarcinoma in Relation to Photodynamic Therapy.International journal of molecular sciences · 2025Review
- Participation of lipids in the tumor response to photodynamic therapy and its exploitation for therapeutic gain.Journal of lipid research · 2025Review
- Acriflavine, an Acridine Derivative for Biomedical Application: Current State of the Art.Journal of medicinal chemistry · 2022Review
- Nanomedicines for Overcoming Cancer Drug Resistance.Pharmaceutics · 2022Review
- Downregulation of topoisomerase 1 and 2 with acriflavine sensitizes bladder cancer cells to cisplatin-based chemotherapy.Molecular biology reports · 2022Article
- DNA topoisomerase inhibition with the HIF inhibitor acriflavine promotes transcription of lncRNAs in endothelial cells.Molecular therapy. Nucleic acids · 2022Article
- Strategies for Improving Photodynamic Therapy Through Pharmacological Modulation of the Immediate Early Stress Response.Methods in molecular biology (Clifton, N.J.) · 2022Review
- Optimal Use of 2',7'-Dichlorofluorescein Diacetate in Cultured Hepatocytes.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Inhibition of the HIF-1 Survival Pathway as a Strategy to Augment Photodynamic Therapy Efficacy.Methods in molecular biology (Clifton, N.J.) · 2022Article
- High-Throughput Examination of Therapy-Induced Alterations in Redox Metabolism in Spheroid and Microtumor Models.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Application of Monolayer Cell Cultures for Investigating Basic Mechanisms of Photodynamic Therapy.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Multi-Functional Liposome: A Powerful Theranostic Nano-Platform Enhancing Photodynamic Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- Analysis and Optimization of Conditions for the Use of 2',7'-Dichlorofluorescein Diacetate in Cultured Hepatocytes.Antioxidants (Basel, Switzerland) · 2021Article
- Tailoring photosensitive ROS for advanced photodynamic therapy.Experimental & molecular medicine · 2021Review
- Hypoxia, endoplasmic reticulum stress and chemoresistance: dangerous liaisons.Journal of experimental & clinical cancer research : CR · 2021Review
- Effect of Photodynamic Therapy on Gemcitabine-Resistant CholangiocarcinomaFrontiers in cell and developmental biology · 2021Article
- Cabozantinib Inhibits Photodynamic Therapy-Induced Auto- and Paracrine MET Signaling in Heterotypic Pancreatic Microtumors.Cancers · 2020Article
- Photodynamic Therapy in Primary Breast Cancer.Journal of clinical medicine · 2020Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPhotodynamic therapy (PDT) induces tumor cell death by oxidative stress and hypoxia but also survival signaling through activation of hypoxia-inducible factor 1 (HIF-1). Since perihilar cholangiocarcinomas are relatively recalcitrant to PDT, the aims were to (1) determine the expression levels of HIF-1-associated proteins in human perihilar cholangiocarcinomas, (2) investigate the role of HIF-1 in PDT-treated human perihilar cholangiocarcinoma cells, and (3) determine whether HIF-1 inhibition reduces survival signaling and enhances PDT efficacy.
resultsIncreased expression of VEGF, CD105, CD31/Ki-67, and GLUT-1 was confirmed in human perihilar cholangiocarcinomas. PDT with liposome-delivered zinc phthalocyanine caused HIF-1α stabilization in SK-ChA-1 cells and increased transcription of HIF-1α downstream genes. Acriflavine was taken up by SK-ChA-1 cells and translocated to the nucleus under hypoxic conditions. Importantly, pretreatment of SK-ChA-1 cells with acriflavine enhanced PDT efficacy via inhibition of HIF-1 and topoisomerases I and II.
methodsThe expression of VEGF, CD105, CD31/Ki-67, and GLUT-1 was determined by immunohistochemistry in human perihilar cholangiocarcinomas. In addition, the response of human perihilar cholangiocarcinoma (SK-ChA-1) cells to PDT with liposome-delivered zinc phthalocyanine was investigated under both normoxic and hypoxic conditions. Acriflavine, a HIF-1α/HIF-1β dimerization inhibitor and a potential dual topoisomerase I/II inhibitor, was evaluated for its adjuvant effect on PDT efficacy.
conclusionsHIF-1, which is activated in human hilar cholangiocarcinomas, contributes to tumor cell survival following PDT in vitro. Combining PDT with acriflavine pretreatment improves PDT efficacy in cultured cells and therefore warrants further preclinical validation for therapy-recalcitrant perihilar cholangiocarcinomas.
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