Low-power photodynamic therapy induces survival signaling in perihilar cholangiocarcinoma cells
| Autor: | Thomas M. van Gulik, Rowan F. van Golen, Esther Nieuwenhuis, Mans Broekgaarden, Ruud Weijer, Esther B. Bulle, Michal Heger, Perry D. Moerland, Aldo Jongejan, Antoine H. C. van Kampen |
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| Přispěvatelé: | Graduate School, Other departments, Epidemiology and Data Science, AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Surgery, CCA -Cancer Center Amsterdam, 02 Surgical specialisms |
| Rok vydání: | 2015 |
| Předmět: |
Male
Cancer Research Pathology medicine.medical_specialty Indoles Cell Survival medicine.medical_treatment Drug delivery system Photodynamic therapy Context (language use) Isoindoles Therapeutic recalcitrance chemistry.chemical_compound Mice Immune system Downregulation and upregulation In vivo Genetics Organometallic Compounds Medicine Animals Humans Photosensitizer Propidium iodide Photosensitizing Agents business.industry Metallated phthalocyanines Gene Expression Profiling Hypoxia-Inducible Factor 1 alpha Subunit In vitro Up-Regulation Gene Expression Regulation Neoplastic Tumor targeting Oncology chemistry Bile Duct Neoplasms Photochemotherapy Zinc Compounds Liposomes Cancer research Non-resectable perihilar cholangiocarcinoma business Klatskin Tumor Signal Transduction Research Article |
| Zdroj: | BMC Cancer BMC cancer, 15(1). BioMed Central |
| ISSN: | 1471-2407 |
| Popis: | Background Photodynamic therapy (PDT) of solid cancers comprises the administration of a photosensitizer followed by illumination of the photosensitizer-replete tumor with laser light. This induces a state of local oxidative stress, culminating in the destruction of tumor tissue and microvasculature and induction of an anti-tumor immune response. However, some tumor types, including perihilar cholangiocarcinoma, are relatively refractory to PDT, which may be attributable to the activation of survival pathways in tumor cells following PDT (i.e., activator protein 1 (AP-1)-, nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB)-, hypoxia-inducible factor 1-alpha (HIF-1α)-, nuclear factor (erythroid-derived 2)-like 2 (NFE2L2)-, and unfolded protein response-mediated pathways). Methods To assess the activation of survival pathways after PDT, human perihilar cholangiocarcinoma (SK-ChA-1) cells were subjected to PDT with zinc phthalocyanine (ZnPC)-encapsulating liposomes. Following 30-minute incubation with liposomes, the cells were either left untreated or treated at low (50 mW) or high (500 mW) laser power (cumulative light dose of 15 J/cm2). Cells were harvested 90 min post-PDT and whole genome expression analysis was performed using Illumina HumanHT-12 v4 expression beadchips. The data were interpreted in the context of the survival pathways. In addition, the safety of ZnPC-encapsulating liposomes was tested both in vitro and in vivo. Results PDT-treated SK-ChA-1 cells exhibited activation of the hypoxia-induced stress response via HIF-1α and initiation of the pro-inflammatory response via NF-кB. PDT at low laser power in particular caused extensive survival signaling, as evidenced by the significant upregulation of HIF-1- (P |
| Databáze: | OpenAIRE |
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