title: Nanoparticle-based hyperthermia distinctly impacts production of ROS, expression of Ki-67, TOP2A, and TPX2, and induction of apoptosis in pancreatic cancer.
abstract: So far, the therapeutic outcome of hyperthermia has shown heterogeneous responses depending on how thermal stress is applied. We studied whether extrinsic heating (EH, hot air) and intrinsic heating (magnetic heating [MH] mediated by nanoparticles) induce distinct effects on pancreatic cancer cells (PANC-1 and BxPC-3 cells). The impact of MH (100 µg magnetic nanoparticles [MNP]/mL; H=23.9 kA/m; f=410 kHz) was always superior to that of EH. The thermal effects were confirmed by the following observations: 1) decreased number of vital cells, 2) altered expression of pro-caspases, and 3) production of reactive oxygen species, and 4) altered mRNA expression of Ki-67, TOP2A, and TPX2. The MH treatment of tumor xenografts significantly (P≤0.05) reduced tumor volumes. This means that different therapeutic outcomes of hyperthermia are related to the different responses cells exert to thermal stress. In particular, intratumoral MH is a valuable tool for the treatment of pancreatic cancers.
authors.affiliation: Department of Experimental Radiology, Institute for Diagnostic and Interventional Radiology, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Ludwig
authors.affiliation: iMdea-Nanociencia, Campus Universitario de Cantoblanco; Nanobiotecnología (iMdea-Nanociencia), Unidad Asociada al Centro Nacional de Biotecnología (CSIC), Madrid, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Teran
authors.affiliation: Department of Experimental Radiology, Institute for Diagnostic and Interventional Radiology, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Teichgraeber
authors.affiliation: Department of Experimental Radiology, Institute for Diagnostic and Interventional Radiology, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hilger
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006979:Hyperthermia, Induced; D019394:Ki-67 Antigen / Q000378:metabolism*; D008280:Magnetics; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry*; D009687:Nuclear Proteins / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D000075223:Poly-ADP-Ribose Binding Proteins; D017382:Reactive Oxygen Species / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D017382:Reactive Oxygen Species; C122167:TPX2 protein, human; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human; C000618812:Top2a protein, mouse
keywords: heat dose; iron oxide nanoparticles; magnetic hyperthermia; nanomedicine; proliferation marker